1387:
1523:. Pembrolizumab has been made accessible to advanced melanoma patients in the UK via UK Early Access to Medicines Scheme (EAMS) in March 2015. It is being used in clinical trials in the US for lung cancer, lymphoma, and mesothelioma. It has had measured success, with little side effects. It is up to the manufacturer of the drug to submit application to the FDA for approval for use in these diseases. On October 2, 2015, Pembrolizumab was approved by FDA for advanced (metastatic) non-small cell lung cancer (NSCLC) patients whose disease has progressed after other treatments.
323:
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CD8+ T cells that are actively infiltrating the tumor tissue. The authors hypothesized that the higher levels of CD8+ T cell infiltration was due to anti-CTLA-4 inhibited the conversion of CD4 T cells to T regulator cells and further reduced T regulatory suppression with anti-PD-1. This combination promoted a more robust inflammatory response to the tumor that reduced the size of the cancer. Most recently, the FDA has approved a combination therapy with both anti-CTLA4 (
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tissue. Repeated administrations with anti-PD-1 were found to be necessary to maintain the therapeutic effects of the treatment. Amyloid fibrils are immunosuppressive and this finding has been separately confirmed by examining the effects of the fibrils in neuroinflammatory diseases. PD-1 counteracts the effects of the fibrils by boosting immune activity and triggering an immune pathway that allows for brain repair.
42:
1460:
expression on the surface on cancer cells plays a significant role. PD-L1 positive tumors were twice as likely to respond to combination treatment. However patients with PD-L1 negative tumors also have limited response to anti-PD1, demonstrating that PD-L1 expression is not an absolute determinant of
1444:
In clinical trials, combination therapy has been shown to be effective in reducing tumor size in patients that are unresponsive to single co-inhibitory blockade, despite increasing levels of toxicity due to anti-CTLA4 treatment. A combination of PD1 and CTLA4 induced up to a ten-fold higher number of
1317:
stimulated T cells with PD-L1-Ig results in reduced T cell proliferation and IFN-γ secretion. IFN-γ is a key pro-inflammatory cytokine that promotes T cell inflammatory activity. Reduced T cell proliferation was also correlated with attenuated IL-2 secretion and together, these data suggest that PD-1
3276:
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia
2226:
Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, Freeman GJ (March 2001). "PD-L2 is a second ligand for PD-1 and inhibits T
1590:
Blocking of PD-1 leads to a reduction in cerebral amyloid-β plaques and improves cognitive performance in mice. Immune blockade of PD-1 evoked an IFN-γ dependent immune response that recruited monocyte-derived macrophages to the brain that were then capable of clearing the amyloid-β plaques from the
1338:
Expression of PD-L1 on tumor cells inhibits anti-tumor activity through engagement of PD-1 on effector T cells. Expression of PD-L1 on tumors is correlated with reduced survival in esophageal, pancreatic and other types of cancers, highlighting this pathway as a target for immunotherapy. Triggering
3896:
Prokunina L, Castillejo-López C, Oberg F, Gunnarsson I, Berg L, Magnusson V, Brookes AJ, Tentler D, Kristjansdóttir H, Gröndal G, Bolstad AI, Svenungsson E, Lundberg I, Sturfelt G, Jönssen A, Truedsson L, Lima G, Alcocer-Varela J, Jonsson R, Gyllensten UB, Harley JB, Alarcón-Segovia D, Steinsson K,
1581:
eradication. T lymphocytes exhibit elevated expression of PD-1 in cases of chronic HIV infection. Heightened presence of the PD-1 receptors corresponds to exhaustion of the HIV specific CD8+ cytotoxic and CD4+ helper T cell populations that are vital in combating the virus. Immune blockade of PD-1
1464:
Higher mutational burden in the tumor is correlated with a greater effect of the anti-PD-1 treatment. In clinical trials, patients who benefited from anti-PD1 treatment had cancers, such as melanoma, bladder cancer, and gastric cancer, that had a median higher average number of mutations than the
1436:
A combination of PD1 and CTLA4 antibodies has been shown to be more effective than either antibody alone in the treatment of a variety of cancers. The effects of the two antibodies do not appear to be redundant. Anti-CTLA4 treatment leads to an enhanced antigen specific T cell dependent immune
68:
4130:
Prokunina L, Padyukov L, Bennet A, de Faire U, Wiman B, Prince J, Alfredsson L, Klareskog L, Alarcón-Riquelme M (June 2004). "Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope".
1334:
viral vector model of chronic infection, Rafi Ahmed's group showed that the PD-1-PD-L1 interaction inhibits activation, expansion and acquisition of effector functions of virus specific CD8 T cells, which can be reversed by blocking the PD-1-PD-L1 interaction.
3598:
Baruch K, Deczkowska A, Rosenzweig N, Tsitsou-Kampeli A, Sharif AM, Matcovitch-Natan O, Kertser A, David E, Amit I, Schwartz M (February 2016). "PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of
Alzheimer's disease".
4351:
Kobayashi M, Kawano S, Hatachi S, Kurimoto C, Okazaki T, Iwai Y, Honjo T, Tanaka Y, Minato N, Komori T, Maeda S, Kumagai S (November 2005). "Enhanced expression of programmed death-1 (PD-1)/PD-L1 in salivary glands of patients with Sjögren's syndrome".
2906:
Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS (November 2014).
3489:
Chew GM, Fujita T, Webb GM, Burwitz BJ, Wu HL, Reed JS, Hammond KB, Clayton KL, Ishii N, Abdel-Mohsen M, Liegler T, Mitchell BI, Hecht FM, Ostrowski M, Shikuma CM, Hansen SG, Maurer M, Korman AJ, Deeks SG, Sacha JB, Ndhlovu LC (January 2016).
2964:
Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggeman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD, Chan TA (December 2014).
4160:
Sanghera DK, Manzi S, Bontempo F, Nestlerode C, Kamboh MI (October 2004). "Role of an intronic polymorphism in the PDCD1 gene with the risk of sporadic systemic lupus erythematosus and the occurrence of antiphospholipid antibodies".
4070:
Prokunina L, Gunnarsson I, Sturfelt G, Truedsson L, Seligman VA, Olson JL, Seldin MF, Criswell LA, Alarcón-Riquelme ME (January 2004). "The systemic lupus erythematosus-associated PDCD1 polymorphism PD1.3A in lupus nephritis".
1329:
T cells suggest that CD8 T cells are more susceptible to inhibition by PD-L1, although this could be dependent on the strength of TCR signaling. Consistent with a role in negatively regulating CD8 T cell responses, using an
1176:
in 1992 discovered and named PD-1. In 1999, the same group demonstrated that mice where PD-1 was knocked down were prone to autoimmune disease and hence concluded that PD-1 was a negative regulator of immune responses.
4198:
Nielsen C, Laustrup H, Voss A, Junker P, Husby S, Lillevang ST (2005). "A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients".
2635:
Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, Hill BJ, Noto A, Ancuta P, Peretz Y, Fonseca SG, Van
Grevenynghe J, Boulassel MR, Bruneau J, Shoukry NH, Routy JP, Douek DC, Haddad EK, Sekaly RP (April 2010).
2173:
Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (October 2000).
4100:
Lin SC, Yen JH, Tsai JJ, Tsai WC, Ou TT, Liu HW, Chen CJ (March 2004). "Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus".
1505:), produced complete or partial responses in non-small-cell lung cancer, melanoma, and renal-cell cancer, in a clinical trial with a total of 296 patients. Colon and pancreatic cancer did not have a response.
2458:
Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N, Honjo T (January 2001). "Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice".
3936:"Program death-1 engagement upon TCR activation has distinct effects on costimulation and cytokine-driven proliferation: attenuation of ICOS, IL-4, and IL-21, but not CD28, IL-7, and IL-15 responses"
4012:
Youngnak P, Kozono Y, Kozono H, Iwai H, Otsuki N, Jin H, Omura K, Yagita H, Pardoll DM, Chen L, Azuma M (August 2003). "Differential binding properties of B7-H1 and B7-DC to programmed death-1".
5307:
4041:
Nielsen C, Hansen D, Husby S, Jacobsen BB, Lillevang ST (December 2003). "Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes".
2543:
Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, Freeman GJ, Ahmed R (February 2006). "Restoring function in exhausted CD8 T cells during chronic viral infection".
4446:
2131:
Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H, Honjo T (May 1996). "Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes".
1465:
patients who did not respond to the therapy. However, the correlation between higher tumor burden and the clinical effectiveness of PD-1 immune blockade is still uncertain.
1892:
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336:
235:
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can be detected in the heart, lung, thymus, spleen, and kidney. PD-L1 is expressed on almost all murine tumor cell lines, including PA1 myeloma, P815 mastocytoma, and
1278:
4250:
Johansson M, Arlestig L, Möller B, Rantapää-Dahlqvist S (June 2005). "Association of a PDCD1 polymorphism with renal manifestations in systemic lupus erythematosus".
2594:
Ohigashi Y, Sho M, Yamada Y, Tsurui Y, Hamada K, Ikeda N, Mizuno T, Yoriki R, Kashizuka H, Yane K, Tsushima F, Otsuki N, Yagita H, Azuma M, Nakajima Y (April 2005).
6483:
5297:
1218:
2836:
Gandini S, Massi D, Mandalà M (April 2016). "PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis".
3803:
Vibhakar R, Juan G, Traganos F, Darzynkiewicz Z, Finger LR (April 1997). "Activation-induced expression of human programmed death-1 gene in T-lymphocytes".
1339:
PD-1, expressed on monocytes and up-regulated upon monocytes activation, by its ligand PD-L1 induces IL-10 production which inhibits CD4 T-cell function.
5277:
4414:
3426:
797:
3897:
Alarcón-Riquelme ME (December 2002). "A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans".
778:
158:
6139:
4463:
4439:
1414:. Many tumor cells express PD-L1, an immunosuppressive PD-1 ligand; inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses
3934:
Bennett F, Luxenberg D, Ling V, Wang IM, Marquette K, Lowe D, Khan N, Veldman G, Jacobs KA, Valge-Archer VE, Collins M, Carreno BM (January 2003).
5870:
1685:
Shinohara T, Taniwaki M, Ishida Y, Kawaichi M, Honjo T (October 1994). "Structure and chromosomal localization of the human PD-1 gene (PDCD1)".
5858:
5636:
2871:
Weber J (October 2010). "Immune checkpoint proteins: a new therapeutic paradigm for cancer--preclinical background: CTLA-4 and PD-1 blockade".
1386:
5922:
5917:
5863:
5643:
4424:
1667:
3492:"TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection"
1649:
6573:
6568:
5376:
5302:
4432:
3691:
Kurnellas MP, Ghosn EE, Schartner JM, Baker J, Rothbard JJ, Negrin RS, Herzenberg LA, Fathman CG, Steinman L, Rothbard JB (December 2015).
1402:
PD-L1, the ligand for PD1, is highly expressed in several cancers and hence the role of PD1 in cancer immune evasion is well established.
3068:"PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors"
6476:
6405:
6400:
6395:
6390:
5317:
3867:
Iwai Y, Okazaki T, Nishimura H, Kawasaki A, Yagita H, Honjo T (October 2002). "Microanatomical localization of PD-1 in human tonsils".
2270:
Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y, Shin T, Tsuchiya H, Pardoll DM, Okumura K, Azuma M, Yagita H (November 2002).
1001:
322:
6370:
2176:"Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation"
1008:
1137:, a new class of drugs that block PD-1, activate the immune system to attack tumors and are used to treat certain types of cancer.
299:
4308:
Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, Linsley PS, Thompson CB, Riley JL (November 2005).
5606:
2027:"Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion"
1725:
4279:
Nielsen C, Ohm-Laursen L, Barington T, Husby S, Lillevang ST (June 2005). "Alternative splice variants of the human PD-1 gene".
5668:
5354:
1636:
1615:
1233:
phosphatases to the cytoplasmic tail of PD-1 upon ligand binding. In addition, PD-1 ligation up-regulates E3-ubiquitin ligases
2520:
2503:
6469:
5813:
5349:
2419:"Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor"
2596:"Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer"
1632:
1100:'s response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing
1529:
is a humanized IgG4 monoclonal antibody against PD-1 which was approved in China in 2018 and in the United States in 2023.
221:
196:
65:
6310:
5782:
5777:
5722:
5456:
4905:
3834:"The human PD-1 gene: complete cDNA, genomic organization, and developmentally regulated expression in B cell progenitors"
1611:
3322:
1509:(Opdivo, Bristol-Myers Squibb) was approved in Japan in July 2014 and by the US FDA in December 2014 to treat metastatic
6004:
5727:
1519:(Keytruda, MK-3475, Merck), which also targets PD-1 receptors, was approved by the FDA in Sept 2014 to treat metastatic
138:
2638:"Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection"
5322:
2316:"Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade"
1342:
In mice, expression of this gene is induced in the thymus when anti-CD3 antibodies are injected and large numbers of
335:
234:
3971:"Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction"
6492:
6034:
4459:
1756:
Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting".
1419:
1206:
1141:
1070:
328:
227:
4900:
2502:
Carter L, Fouser LA, Jussif J, Fitz L, Deng B, Wood CR, Collins M, Honjo T, Freeman GJ, Carreno BM (March 2002).
1489:
1221:
and an immunoreceptor tyrosine-based switch motif, which suggests that PD-1 negatively regulates T-cell receptor
6084:
4979:
4384:
2133:
1924:"Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death"
1469:
1355:
1237:
and c-CBL that trigger T cell receptor down-modulation. PD-1 is expressed on the surface of activated T cells,
846:
146:
3752:"Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease"
1456:
The molecular factors and receptors necessary making a tumor receptive to anti-PD1 treatment remains unknown.
2378:"PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells"
1281:
treatment, and on T cells and B cells upon TCR and B cell receptor signaling, whereas in resting mice, PD-L1
6048:
1840:
Fife BT, Pauken KE (January 2011). "The role of the PD-1 pathway in autoimmunity and peripheral tolerance".
1395:
827:
823:
3343:
6578:
5391:
5386:
5381:
5371:
4678:
4606:
1351:
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resulted in restoration of T cell inflammatory phenotype necessary to combat the progression of disease.
4735:
4653:
4236:
1430:
1403:
1254:
1145:
1085:
1301:
Several lines of evidence suggest that PD-1 and its ligands negatively regulate immune responses. PD-1
3832:
Finger LR, Pu J, Wasserman R, Vibhakar R, Louie E, Hardy RR, Burrows PD, Billips LG (September 1997).
6496:
5972:
5685:
3704:
3134:
3079:
2920:
2552:
2468:
2327:
1849:
1533:
1502:
1391:
210:
6461:
2084:"PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells"
125:
5999:
5818:
1105:
4380:
5406:
5140:
4224:
4186:
3922:
3624:
3158:
2576:
2252:
2064:
1873:
1363:
1306:
1274:
170:
1541:
984:
963:
937:
916:
1245:, suggesting that compared to CTLA-4, PD-1 more broadly negatively regulates immune responses.
4391:
4361:
4339:
4296:
4267:
4216:
4178:
4148:
4118:
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4029:
4000:
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3914:
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2150:
2113:
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2007:
1953:
1865:
1822:
1773:
1702:
1573:
Drugs targeting PD-1 in combination with other negative immune checkpoint receptors, such as (
1370:
1128:
1112:
118:
58:
2504:"PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2"
6179:
5912:
5833:
5396:
4589:
4515:
4329:
4321:
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4208:
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2845:
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2798:
2755:
2747:
2734:
Müller T, Braun M, Dietrich D, Aktekin S, Höft S, Kristiansen G, et al. (August 2017).
2706:
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2515:
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Karwacz K, Bricogne C, MacDonald D, Arce F, Bennett CL, Collins M, Escors D (October 2011).
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1997:
1987:
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1935:
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1812:
1804:
1765:
1694:
1473:
1438:
1326:
1314:
1293:. PD-L2 expression is more restricted and is expressed mainly by DCs and a few tumor lines.
1290:
1186:
1173:
415:
346:
290:
245:
6548:
3016:"CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition"
2909:"Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients"
1494:
A number of cancer immunotherapy agents that target the PD-1 receptor have been developed.
573:
166:
6239:
4775:
4770:
4693:
1222:
1214:
390:
3750:
Kurnellas MP, Schartner JM, Fathman CG, Jagger A, Steinman L, Rothbard JB (August 2014).
6553:
3708:
3138:
3083:
2924:
2556:
2472:
2376:
Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T, Gajewski TF (February 2004).
2331:
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1853:
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4760:
4334:
4309:
3995:
3970:
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3751:
3727:
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3668:
3643:
3572:
3546:"Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options"
3545:
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3466:
3441:
3303:
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3228:
3102:
3067:
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3015:
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2735:
2711:
2686:
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2200:
2175:
2108:
2083:
2002:
1975:
1939:
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1792:
1310:
1270:
1134:
4025:
3880:
3850:
3833:
2435:
2418:
2350:
2315:
1948:
1923:
1769:
712:
707:
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697:
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682:
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672:
667:
651:
646:
641:
636:
615:
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5994:
5451:
4542:
4418:
4400:
4325:
4054:
2884:
2849:
2580:
1861:
1808:
1516:
1480:"for their discovery of cancer therapy by inhibition of negative immune regulation".
1407:
1322:
1302:
1210:
1097:
602:
4228:
3926:
3693:"Amyloid fibrils activate B-1a lymphocytes to ameliorate inflammatory brain disease"
3628:
3162:
2256:
2068:
1877:
6350:
5658:
5648:
5179:
5145:
4190:
3361:
3229:"Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy"
1545:
1477:
1286:
1266:
1169:
408:
187:
150:
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2595:
2394:
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3659:
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1313:
on the C57BL/6 and BALB/c backgrounds, respectively. In vitro, treatment of anti-
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5461:
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1672:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1654:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1537:
1526:
4212:
3952:
3935:
3697:
Proceedings of the
National Academy of Sciences of the United States of America
3403:
3386:
3072:
Proceedings of the
National Academy of Sciences of the United States of America
2775:- "Figure 1 - available via license: Creative Commons Attribution 3.0 Unported"
2320:
Proceedings of the
National Academy of Sciences of the United States of America
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4940:
4935:
4790:
4574:
4174:
3562:
3457:
3125:
Sliwkowski MX, Mellman I (September 2013). "Antibody therapeutics in cancer".
2787:"PD-L1 expression in human cancers and its association with clinical outcomes"
2751:
2736:"PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma"
2042:
1553:
1446:
1242:
1234:
1190:
1124:
307:
204:
154:
2702:
2146:
1992:
6129:
6124:
6119:
6109:
6104:
6099:
6094:
4310:"CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms"
3717:
3644:"Amyloid fibrils composed of hexameric peptides attenuate neuroinflammation"
3146:
3092:
1612:
ENSG00000276977 GRCh38: Ensembl release 89: ENSG00000188389, ENSG00000276977
1506:
1498:
1450:
1429:
therapeutics have emerged as important tumor treatments within the field of
1347:
1343:
1321:
Experiments using PD-L1 transfected DCs and PD-1 expressing transgenic (Tg)
1165:
1116:
742:
620:
551:
429:
374:
361:
273:
260:
162:
6544:
What I Talk about When I Talk about the
Discovery of PD-1 (Yasumasa Ishida)
4365:
4343:
4300:
4271:
4220:
4182:
4152:
4122:
4092:
4062:
4033:
4004:
3961:
3918:
3888:
3816:
3785:
3736:
3677:
3620:
3581:
3527:
3475:
3412:
3312:
3262:
3206:
3154:
3111:
3049:
3000:
2950:
2892:
2857:
2822:
2769:
2720:
2671:
2621:
2572:
2529:
2488:
2444:
2403:
2359:
2340:
2314:
Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N (September 2002).
2297:
2248:
2209:
2191:
2117:
2099:
2060:
2011:
1869:
1826:
1777:
1698:
1115:
and guards against autoimmunity through two mechanisms. First, it promotes
3859:
3824:
3294:
2982:
2154:
1957:
1706:
1048:
1043:
6543:
6435:
6335:
6149:
6134:
5337:
5332:
5240:
4930:
3986:
3767:
3279:"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer"
1893:"New Bristol-Myers Drug Helped Skin-Cancer Patients in Trial Live Longer"
1549:
1520:
1510:
1032:
891:
872:
3642:
Kurnellas MP, Adams CM, Sobel RA, Steinman L, Rothbard JB (April 2013).
3244:
2932:
2803:
2564:
1398:, demonstrating negative (A), low (B), and high (C) PD-L1 protein levels
1358:. These studies suggest that this gene product may also be important in
6385:
6380:
6375:
6275:
6089:
6079:
5906:
5885:
5880:
5848:
5653:
5573:
5568:
5563:
5558:
5553:
5471:
5164:
5004:
4999:
4994:
4989:
4984:
4455:
4405:
4395:
1120:
1108:, but it can also prevent the immune system from killing cancer cells.
1074:
858:
809:
129:, CD279, PD-1, PD1, SLEB2, hPD-1, hPD-l, hSLE1, Programmed cell death 1
4263:
4144:
4114:
4084:
1213:
region and an intracellular tail. The intracellular tail contains two
95:
91:
87:
6520:
6325:
6285:
6270:
6254:
6249:
6229:
6224:
6159:
5967:
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5705:
5673:
5537:
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5481:
5441:
5401:
5267:
5245:
5204:
5128:
5123:
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4972:
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4962:
4910:
4895:
4765:
4755:
4718:
4713:
4631:
4626:
2521:
10.1002/1521-4141(200203)32:3<634::AID-IMMU634>3.0.CO;2-9
1557:
1426:
1411:
1359:
1350:. Mice deficient for this gene bred on a BALB/c background developed
1238:
1230:
1202:
1198:
1101:
1093:
1089:
1016:
764:
17:
3612:
2967:"Genetic basis for clinical response to CTLA-4 blockade in melanoma"
2653:
2272:"Expression of programmed death 1 ligands by murine T cells and APC"
3910:
1976:"The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation"
6525:
6450:
6425:
6345:
6340:
6330:
6320:
6305:
6300:
6295:
6280:
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6219:
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5838:
5797:
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5710:
5690:
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5411:
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5292:
5287:
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5260:
5255:
5235:
5230:
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5220:
5174:
5066:
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4857:
4852:
4847:
4842:
4837:
4832:
4807:
4785:
4780:
4673:
4599:
4594:
4584:
3969:
Wang S, Bajorath J, Flies DB, Dong H, Honjo T, Chen L (May 2003).
2240:
1574:
1457:
1385:
1369:
Overexpression of PD1 on CD8+ T cells is one of the indicators of
1262:
1258:
1226:
1153:
1149:
727:
723:
6530:
6515:
6510:
6445:
6440:
6430:
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6410:
6365:
6355:
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5792:
5772:
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5631:
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5016:
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4885:
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4797:
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4708:
4703:
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4520:
4503:
4498:
4493:
4488:
1331:
1282:
1194:
1081:
142:
6465:
4428:
3344:"FDA approves Keytruda for advanced non-small cell lung cancer"
582:
5957:
4569:
4557:
4552:
4547:
4537:
4510:
4478:
2417:
Nishimura H, Nose M, Hiai H, Minato N, Honjo T (August 1999).
1578:
1205:
regulators. The protein's structure includes an extracellular
1418:
and mediate preclinical antitumor activity. This is known as
4390:
Overview of all the structural information available in the
3442:"Role of PD-1 in HIV pathogenesis and as target for therapy"
3427:"FDA approves toripalimab-tpzi for nasopharyngeal carcinoma"
1144:
and is expressed on T cells and pro-B cells. PD-1 binds two
1532:
Drugs in early stage development targeting PD-1 receptors (
3544:
Velu V, Shetty RD, Larsson M, Shankar EM (February 2015).
3066:
Curran MA, Montalvo W, Yagita H, Allison JP (March 2010).
3362:"Toripalimab - Shanghai Junshi Biosciences - AdisInsight"
3227:
Topalian SL, Taube JM, Anders RA, Pardoll DM (May 2016).
1922:
Ishida Y, Agata Y, Shibahara K, Honjo T (November 1992).
1425:
Combination therapy using both anti-PD1 along with anti-
1269:
family. PD-L1 protein is upregulated on macrophages and
398:
3181:"Oncology meets immunology: the cancer-immunity cycle"
2687:"Overcoming T cell exhaustion in infection and cancer"
3348:
563:
3429:. US Food and Drug Administration. October 27, 2023.
1140:
PD-1 is a cell surface receptor that belongs to the
6503:
6263:
6057:
5806:
5490:
5213:
4873:
4471:
4014:
977:
956:
930:
909:
3321:
1628:
1626:
1624:
1607:
1605:
1603:
1577:), may augment immune responses and/or facilitate
3593:
3591:
345:
244:
3277:GD, Gupta A, Wigginton JM, Sznol M (June 2012).
3222:
3220:
3218:
3216:
2221:
2219:
1793:"The PD-1 pathway in tolerance and autoimmunity"
3174:
3172:
2168:
2166:
2164:
1974:Bardhan K, Anagnostou T, Boussiotis VA (2016).
1969:
1967:
1437:reaction while anti-PD-1 appears to reactivate
688:positive regulation of T cell apoptotic process
1917:
1915:
1913:
1791:Francisco LM, Sage PT, Sharpe AH (July 2010).
1633:GRCm38: Ensembl release 89: ENSMUSG00000026285
1219:immunoreceptor tyrosine-based inhibitory motif
6477:
4440:
4241:: CS1 maint: DOI inactive as of April 2024 (
3061:
3059:
2371:
2369:
1362:function and contribute to the prevention of
8:
2785:Wang X, Teng F, Kong L, Yu J (August 2016).
2309:
2307:
1726:"Entrez Gene: PDCD1 programmed cell death 1"
1225:signals. This is consistent with binding of
6484:
6470:
6462:
4447:
4433:
4425:
4415:United States National Library of Medicine
3539:
3537:
1842:Annals of the New York Academy of Sciences
1131:(anti-inflammatory, suppressive T cells).
738:
698:negative regulation of tolerance induction
598:
386:
285:
182:
76:
4464:list of human clusters of differentiation
4404:(Programmed cell death protein 1) at the
4383:at the U.S. National Library of Medicine
4333:
3994:
3951:
3849:
3775:
3726:
3716:
3667:
3571:
3561:
3517:
3507:
3465:
3402:
3302:
3252:
3196:
3101:
3091:
3039:
2990:
2940:
2812:
2802:
2759:
2710:
2661:
2611:
2519:
2434:
2393:
2349:
2339:
2287:
2199:
2107:
2050:
2001:
1991:
1947:
1816:
1410:are being developed for the treatment of
4413:This article incorporates text from the
3323:"Drug Helps Defense System Fight Cancer"
3014:Buchbinder EI, Desai A (February 2016).
1720:
1718:
1716:
683:negative regulation of apoptotic process
668:positive regulation of apoptotic process
2838:Critical Reviews in Oncology/Hematology
1599:
1373:(e.g. in chronic infection or cancer).
1318:negatively regulates T cell responses.
4234:
3440:Porichis F, Kaufmann DE (March 2012).
1305:have been shown to develop lupus-like
31:
6549:PD-1_Project PD-1 project - Honjo Lab
3020:American Journal of Clinical Oncology
1560:) target the similar PD-L1 receptor.
1104:inflammatory activity. This prevents
350:
311:
306:
249:
208:
203:
7:
3975:The Journal of Experimental Medicine
3756:The Journal of Experimental Medicine
3387:"Toripalimab: First Global Approval"
2180:The Journal of Experimental Medicine
1751:
1749:
1747:
1745:
1743:
1741:
1739:
1737:
1735:
6554:PD-1プロジェクト(in Japanese) - Honjo Lab
3283:The New England Journal of Medicine
2971:The New England Journal of Medicine
1193:. PD-1 is a member of the extended
1940:10.1002/j.1460-2075.1992.tb05481.x
1497:One such anti-PD-1 antibody drug,
1164:In a screen for genes involved in
1127:. Second, it reduces apoptosis in
1096:that has a role in regulating the
974:
953:
927:
906:
882:
863:
837:
814:
788:
769:
673:multicellular organism development
568:
486:
424:
403:
25:
2025:Blank C, Mackensen A (May 2007).
27:Mammalian protein found in humans
4326:10.1128/MCB.25.21.9543-9553.2005
4055:10.1046/j.1399-0039.2003.00136.x
3179:Chen DS, Mellman I (July 2013).
2885:10.1053/j.seminoncol.2010.09.005
2850:10.1016/j.critrevonc.2016.02.001
2031:Cancer Immunology, Immunotherapy
1862:10.1111/j.1749-6632.2010.05919.x
1809:10.1111/j.1600-065X.2010.00923.x
1390:PD-L1 expression by chromogenic
652:external side of plasma membrane
572:
334:
327:
321:
298:
233:
226:
220:
195:
40:
3320:Andrew Pollack (June 1, 2012).
1061:Programmed cell death protein 1
4314:Molecular and Cellular Biology
3648:Science Translational Medicine
2508:European Journal of Immunology
1554:Merck KGaA, Darmstadt, Germany
1544:(Bristol Myers Squibb). Both
1461:the effectiveness of therapy.
1441:ability to lyse cancer cells.
1406:targeting PD-1 that boost the
637:integral component of membrane
583:More reference expression data
552:More reference expression data
1:
4293:10.1016/j.cellimm.2005.07.007
4026:10.1016/S0006-291X(03)01257-9
3881:10.1016/S0165-2478(02)00088-3
3851:10.1016/S0378-1119(97)00260-6
2685:Pauken KE, Wherry EJ (2015).
2613:10.1158/1078-0432.CCR-04-1469
2436:10.1016/S1074-7613(00)80089-8
2395:10.1158/0008-5472.CAN-03-3259
1770:10.1016/s1470-2045(17)30607-1
319:
218:
3660:10.1126/scitranslmed.3005681
3509:10.1371/journal.ppat.1005349
3198:10.1016/j.immuni.2013.07.012
3032:10.1097/COC.0000000000000239
2481:10.1126/science.291.5502.319
2289:10.4049/jimmunol.169.10.5538
6574:Clusters of differentiation
6569:Genes on human chromosome 2
4460:clusters of differentiation
4354:The Journal of Rheumatology
1265:, which are members of the
1119:(programmed cell death) of
6595:
6493:Immunoglobulin superfamily
4213:10.1191/0961203303lu1052oa
3953:10.4049/jimmunol.170.2.711
3805:Experimental Cell Research
3404:10.1007/s40265-019-01076-2
1487:
1420:immune checkpoint blockade
1394:in cases of head and neck
1142:immunoglobulin superfamily
1071:cluster of differentiation
621:signal transducer activity
468:mucosa of transverse colon
4175:10.1007/s00439-004-1172-0
3563:10.1186/s12977-015-0144-x
3458:10.1007/s11904-011-0106-4
2752:10.18632/oncotarget.17547
2043:10.1007/s00262-006-0272-1
1668:"Mouse PubMed Reference:"
1650:"Human PubMed Reference:"
1490:PD-1 and PD-L1 inhibitors
1077:encoded in humans by the
1047:
1042:
1038:
1031:
1015:
1002:Chr 2: 241.85 – 241.86 Mb
996:
981:
960:
949:
934:
913:
902:
889:
885:
870:
866:
857:
844:
840:
821:
817:
808:
795:
791:
776:
772:
763:
748:
741:
737:
721:
601:
597:
580:
571:
562:
549:
498:
489:
436:
427:
397:
389:
385:
368:
355:
318:
297:
288:
284:
267:
254:
217:
194:
185:
181:
136:
133:
123:
116:
111:
84:
79:
62:
57:
52:
48:
39:
34:
4385:Medical Subject Headings
4252:Arthritis and Rheumatism
4133:Arthritis and Rheumatism
4103:Arthritis and Rheumatism
4073:Arthritis and Rheumatism
3446:Current HIV/AIDS Reports
3366:adisinsight.springer.com
2703:10.1016/j.it.2015.02.008
2600:Clinical Cancer Research
2134:International Immunology
1993:10.3389/fimmu.2016.00550
1891:Loftus P (16 Nov 2014).
1540:(CT-011, Cure Tech) and
1470:Nobel Prize for Medicine
1356:congestive heart failure
4215:(inactive 2024-04-12).
3718:10.1073/pnas.1521206112
3147:10.1126/science.1241145
3093:10.1073/pnas.0915174107
2791:OncoTargets and Therapy
2088:EMBO Molecular Medicine
1980:Frontiers in Immunology
1585:
1548:(MPDL3280A, Roche) and
1396:squamous cell carcinoma
1009:Chr 1: 93.97 – 93.98 Mb
693:humoral immune response
472:upper lobe of left lung
3817:10.1006/excr.1997.3493
3233:Nature Reviews. Cancer
2341:10.1073/pnas.192461099
2192:10.1084/jem.192.7.1027
2147:10.1093/intimm/8.5.765
2100:10.1002/emmm.201100165
1699:10.1006/geno.1994.1562
1484:Anti-PD-1 therapeutics
1399:
1352:dilated cardiomyopathy
514:mesenteric lymph nodes
6497:CD28 family receptors
3940:Journal of Immunology
3295:10.1056/NEJMoa1200690
2983:10.1056/nejmoa1406498
2276:Journal of Immunology
1797:Immunological Reviews
1534:checkpoint inhibitors
1431:checkpoint inhibition
1404:Monoclonal antibodies
1389:
1377:Clinical significance
1209:domain followed by a
1123:-specific T-cells in
1086:cell surface receptor
703:immune system process
4381:PDCD1+protein,+human
3987:10.1084/jem.20021752
3768:10.1084/jem.20140107
2873:Seminars in Oncology
2691:Trends in Immunology
1758:The Lancet. Oncology
1503:Bristol Myers Squibb
1392:immunohistochemistry
1289:upon treatment with
1273:(DC) in response to
1217:sites located in an
678:T cell costimulation
313:Chromosome 1 (mouse)
211:Chromosome 2 (human)
80:List of PDB id codes
53:Available structures
4281:Cellular Immunology
3709:2015PNAS..11215016K
3385:Keam, S.J. (2019).
3245:10.1038/nrc.2016.36
3139:2013Sci...341.1192S
3084:2010PNAS..107.4275C
2933:10.1038/nature14011
2925:2014Natur.515..563H
2804:10.2147/OTT.S105862
2746:(32): 52889–52900.
2565:10.1038/nature04444
2557:2006Natur.439..682B
2473:2001Sci...291..319N
2332:2002PNAS...9912293I
1897:Wall Street Journal
1854:2011NYASA1217...45F
1586:Alzheimer's disease
1453:) in October 2015.
1364:autoimmune diseases
1168:, Yasumasa Ishida,
1106:autoimmune diseases
713:signal transduction
4417:, which is in the
3869:Immunology Letters
3328:The New York Times
2227:cell activation".
1400:
1307:glomerulonephritis
1172:and colleagues at
1129:regulatory T cells
847:ENSMUSG00000026285
661:Biological process
630:Cellular component
609:Molecular function
6539:
6538:
6459:
6458:
4264:10.1002/art.21058
4145:10.1002/art.20280
4115:10.1002/art.20040
4085:10.1002/art.11442
3350:. 2 October 2015.
2229:Nature Immunology
1764:(12): e731–e741.
1371:T-cell exhaustion
1185:PD-1 is a type I
1113:immune checkpoint
1058:
1057:
1054:
1053:
1027:
1026:
992:
991:
971:
970:
945:
944:
924:
923:
898:
897:
879:
878:
853:
852:
834:
833:
804:
803:
785:
784:
733:
732:
708:apoptotic process
593:
592:
589:
588:
558:
557:
545:
544:
483:
482:
381:
380:
280:
279:
175:PDCD1 - orthologs
107:
106:
103:
102:
63:Ortholog search:
16:(Redirected from
6586:
6486:
6479:
6472:
6463:
4449:
4442:
4435:
4426:
4369:
4347:
4337:
4304:
4275:
4246:
4240:
4232:
4194:
4156:
4126:
4096:
4066:
4037:
4008:
3998:
3965:
3955:
3930:
3892:
3863:
3853:
3828:
3790:
3789:
3779:
3747:
3741:
3740:
3730:
3720:
3703:(49): 15016–23.
3688:
3682:
3681:
3671:
3654:(179): 179ra42.
3639:
3633:
3632:
3595:
3586:
3585:
3575:
3565:
3541:
3532:
3531:
3521:
3511:
3486:
3480:
3479:
3469:
3437:
3431:
3430:
3423:
3417:
3416:
3406:
3382:
3376:
3375:
3373:
3372:
3358:
3352:
3351:
3340:
3334:
3331:
3325:
3316:
3306:
3273:
3267:
3266:
3256:
3224:
3211:
3210:
3200:
3176:
3167:
3166:
3133:(6151): 1192–8.
3122:
3116:
3115:
3105:
3095:
3063:
3054:
3053:
3043:
3011:
3005:
3004:
2994:
2961:
2955:
2954:
2944:
2903:
2897:
2896:
2868:
2862:
2861:
2833:
2827:
2826:
2816:
2806:
2782:
2776:
2773:
2763:
2731:
2725:
2724:
2714:
2682:
2676:
2675:
2665:
2632:
2626:
2625:
2615:
2591:
2585:
2584:
2540:
2534:
2533:
2523:
2499:
2493:
2492:
2467:(5502): 319–22.
2455:
2449:
2448:
2438:
2414:
2408:
2407:
2397:
2373:
2364:
2363:
2353:
2343:
2311:
2302:
2301:
2291:
2267:
2261:
2260:
2223:
2214:
2213:
2203:
2170:
2159:
2158:
2128:
2122:
2121:
2111:
2079:
2073:
2072:
2054:
2022:
2016:
2015:
2005:
1995:
1971:
1962:
1961:
1951:
1928:The EMBO Journal
1919:
1908:
1907:
1905:
1903:
1888:
1882:
1881:
1837:
1831:
1830:
1820:
1788:
1782:
1781:
1753:
1730:
1729:
1722:
1711:
1710:
1682:
1676:
1675:
1664:
1658:
1657:
1646:
1640:
1630:
1619:
1609:
1449:) and anti-PD1 (
1187:membrane protein
1174:Kyoto University
1073:279). PD-1 is a
1040:
1039:
1011:
1004:
987:
975:
966:
954:
950:RefSeq (protein)
940:
928:
919:
907:
883:
864:
838:
815:
789:
770:
739:
599:
585:
576:
569:
554:
494:
492:Top expressed in
487:
432:
430:Top expressed in
425:
404:
387:
377:
364:
353:
338:
331:
325:
314:
302:
286:
276:
263:
252:
237:
230:
224:
213:
199:
183:
177:
128:
121:
98:
77:
71:
50:
49:
44:
32:
21:
6594:
6593:
6589:
6588:
6587:
6585:
6584:
6583:
6559:
6558:
6540:
6535:
6499:
6490:
6460:
6455:
6259:
6053:
5802:
5486:
5209:
4869:
4467:
4453:
4377:
4372:
4360:(11): 2156–63.
4350:
4320:(21): 9543–53.
4307:
4278:
4249:
4233:
4197:
4159:
4129:
4099:
4069:
4043:Tissue Antigens
4040:
4011:
3968:
3933:
3899:Nature Genetics
3895:
3866:
3844:(1–2): 177–87.
3831:
3802:
3798:
3796:Further reading
3793:
3749:
3748:
3744:
3690:
3689:
3685:
3641:
3640:
3636:
3613:10.1038/nm.4022
3601:Nature Medicine
3597:
3596:
3589:
3543:
3542:
3535:
3502:(1): e1005349.
3488:
3487:
3483:
3439:
3438:
3434:
3425:
3424:
3420:
3384:
3383:
3379:
3370:
3368:
3360:
3359:
3355:
3342:
3341:
3337:
3319:
3289:(26): 2443–54.
3275:
3274:
3270:
3226:
3225:
3214:
3178:
3177:
3170:
3124:
3123:
3119:
3065:
3064:
3057:
3013:
3012:
3008:
2977:(23): 2189–99.
2963:
2962:
2958:
2919:(7528): 563–7.
2905:
2904:
2900:
2870:
2869:
2865:
2835:
2834:
2830:
2784:
2783:
2779:
2774:
2733:
2732:
2728:
2684:
2683:
2679:
2654:10.1038/nm.2106
2642:Nature Medicine
2634:
2633:
2629:
2593:
2592:
2588:
2551:(7077): 682–7.
2542:
2541:
2537:
2501:
2500:
2496:
2457:
2456:
2452:
2416:
2415:
2411:
2382:Cancer Research
2375:
2374:
2367:
2326:(19): 12293–7.
2313:
2312:
2305:
2282:(10): 5538–45.
2269:
2268:
2264:
2225:
2224:
2217:
2172:
2171:
2162:
2130:
2129:
2125:
2081:
2080:
2076:
2024:
2023:
2019:
1973:
1972:
1965:
1934:(11): 3887–95.
1921:
1920:
1911:
1901:
1899:
1890:
1889:
1885:
1839:
1838:
1834:
1790:
1789:
1785:
1755:
1754:
1733:
1724:
1723:
1714:
1684:
1683:
1679:
1666:
1665:
1661:
1648:
1647:
1643:
1631:
1622:
1610:
1601:
1597:
1588:
1571:
1566:
1492:
1486:
1474:James P Allison
1472:was awarded to
1384:
1379:
1299:
1271:dendritic cells
1251:
1215:phosphorylation
1183:
1162:
1135:PD-1 inhibitors
1049:View/Edit Mouse
1044:View/Edit Human
1007:
1000:
997:Location (UCSC)
983:
962:
936:
915:
828:ENSG00000276977
826:
824:ENSG00000188389
717:
656:
642:plasma membrane
625:
616:protein binding
581:
550:
541:
536:
532:
528:
524:
520:
516:
512:
508:
504:
490:
479:
474:
470:
466:
462:
458:
454:
450:
446:
442:
428:
372:
359:
351:
341:
340:
339:
332:
312:
289:Gene location (
271:
258:
250:
240:
239:
238:
231:
209:
186:Gene location (
137:
124:
117:
86:
64:
28:
23:
22:
15:
12:
11:
5:
6592:
6590:
6582:
6581:
6576:
6571:
6561:
6560:
6557:
6556:
6551:
6546:
6537:
6536:
6534:
6533:
6528:
6523:
6518:
6513:
6507:
6505:
6501:
6500:
6491:
6489:
6488:
6481:
6474:
6466:
6457:
6456:
6454:
6453:
6448:
6443:
6438:
6433:
6428:
6423:
6418:
6413:
6408:
6403:
6398:
6393:
6388:
6383:
6378:
6373:
6368:
6363:
6358:
6353:
6348:
6343:
6338:
6333:
6328:
6323:
6318:
6313:
6308:
6303:
6298:
6293:
6288:
6283:
6278:
6273:
6267:
6265:
6261:
6260:
6258:
6257:
6252:
6247:
6242:
6237:
6232:
6227:
6222:
6217:
6212:
6207:
6202:
6197:
6192:
6187:
6182:
6177:
6172:
6167:
6162:
6157:
6152:
6147:
6142:
6137:
6132:
6127:
6122:
6117:
6112:
6107:
6102:
6097:
6092:
6087:
6082:
6077:
6072:
6067:
6061:
6059:
6055:
6054:
6052:
6051:
6046:
6037:
6032:
6027:
6022:
6017:
6012:
6007:
6002:
5997:
5992:
5991:
5990:
5985:
5975:
5970:
5965:
5960:
5955:
5950:
5945:
5940:
5935:
5930:
5925:
5920:
5915:
5910:
5904:
5895:
5890:
5889:
5888:
5883:
5873:
5868:
5867:
5866:
5861:
5851:
5846:
5841:
5836:
5831:
5826:
5821:
5816:
5810:
5808:
5804:
5803:
5801:
5800:
5795:
5790:
5785:
5780:
5775:
5770:
5765:
5760:
5755:
5750:
5745:
5740:
5735:
5730:
5725:
5720:
5715:
5714:
5713:
5708:
5698:
5693:
5688:
5683:
5682:
5681:
5676:
5671:
5661:
5656:
5651:
5646:
5641:
5640:
5639:
5634:
5624:
5619:
5614:
5609:
5604:
5599:
5594:
5593:
5592:
5587:
5577:
5571:
5566:
5561:
5556:
5547:
5542:
5541:
5540:
5535:
5530:
5520:
5515:
5510:
5505:
5500:
5494:
5492:
5488:
5487:
5485:
5484:
5479:
5474:
5469:
5464:
5459:
5454:
5449:
5444:
5439:
5434:
5429:
5424:
5419:
5414:
5409:
5404:
5399:
5394:
5389:
5384:
5379:
5374:
5369:
5364:
5359:
5358:
5357:
5352:
5342:
5341:
5340:
5335:
5325:
5320:
5315:
5310:
5305:
5300:
5295:
5290:
5285:
5280:
5275:
5270:
5265:
5264:
5263:
5258:
5248:
5243:
5238:
5233:
5228:
5223:
5217:
5215:
5211:
5210:
5208:
5207:
5202:
5197:
5192:
5187:
5182:
5177:
5172:
5167:
5158:
5153:
5148:
5143:
5138:
5133:
5132:
5131:
5126:
5121:
5116:
5111:
5106:
5096:
5091:
5086:
5081:
5076:
5071:
5070:
5069:
5064:
5054:
5049:
5044:
5039:
5034:
5029:
5024:
5019:
5014:
5013:
5012:
5007:
5002:
4997:
4992:
4987:
4977:
4976:
4975:
4970:
4965:
4955:
4950:
4949:
4948:
4943:
4938:
4928:
4923:
4918:
4913:
4908:
4903:
4898:
4893:
4888:
4883:
4877:
4875:
4871:
4870:
4868:
4867:
4862:
4861:
4860:
4855:
4850:
4845:
4840:
4835:
4825:
4820:
4815:
4810:
4805:
4800:
4795:
4794:
4793:
4788:
4783:
4778:
4768:
4763:
4758:
4753:
4748:
4743:
4738:
4733:
4728:
4723:
4722:
4721:
4716:
4706:
4701:
4696:
4691:
4686:
4681:
4676:
4671:
4666:
4661:
4656:
4651:
4646:
4641:
4636:
4635:
4634:
4629:
4619:
4614:
4609:
4604:
4603:
4602:
4597:
4592:
4587:
4577:
4572:
4567:
4566:
4565:
4555:
4550:
4545:
4540:
4535:
4534:
4533:
4528:
4523:
4513:
4508:
4507:
4506:
4501:
4496:
4491:
4486:
4475:
4473:
4469:
4468:
4454:
4452:
4451:
4444:
4437:
4429:
4410:
4409:
4388:
4376:
4375:External links
4373:
4371:
4370:
4348:
4305:
4276:
4247:
4195:
4163:Human Genetics
4157:
4127:
4097:
4067:
4038:
4009:
3981:(9): 1083–91.
3966:
3931:
3911:10.1038/ng1020
3893:
3864:
3829:
3799:
3797:
3794:
3792:
3791:
3762:(9): 1847–56.
3742:
3683:
3634:
3587:
3533:
3496:PLOS Pathogens
3481:
3432:
3418:
3397:(5): 573–578.
3377:
3353:
3335:
3333:
3332:
3268:
3212:
3168:
3117:
3078:(9): 4275–80.
3055:
3006:
2956:
2898:
2863:
2828:
2777:
2726:
2677:
2627:
2606:(8): 2947–53.
2586:
2535:
2494:
2450:
2409:
2365:
2303:
2262:
2215:
2186:(7): 1027–34.
2160:
2123:
2094:(10): 581–92.
2074:
2017:
1963:
1909:
1883:
1832:
1783:
1731:
1712:
1677:
1659:
1641:
1620:
1598:
1596:
1593:
1587:
1584:
1570:
1567:
1565:
1564:Animal studies
1562:
1488:Main article:
1485:
1482:
1383:
1380:
1378:
1375:
1354:and died from
1311:cardiomyopathy
1298:
1295:
1250:
1247:
1182:
1179:
1161:
1158:
1056:
1055:
1052:
1051:
1046:
1036:
1035:
1029:
1028:
1025:
1024:
1022:
1020:
1013:
1012:
1005:
998:
994:
993:
990:
989:
979:
978:
972:
969:
968:
958:
957:
951:
947:
946:
943:
942:
932:
931:
925:
922:
921:
911:
910:
904:
900:
899:
896:
895:
887:
886:
880:
877:
876:
868:
867:
861:
855:
854:
851:
850:
842:
841:
835:
832:
831:
819:
818:
812:
806:
805:
802:
801:
793:
792:
786:
783:
782:
774:
773:
767:
761:
760:
755:
750:
746:
745:
735:
734:
731:
730:
719:
718:
716:
715:
710:
705:
700:
695:
690:
685:
680:
675:
670:
664:
662:
658:
657:
655:
654:
649:
644:
639:
633:
631:
627:
626:
624:
623:
618:
612:
610:
606:
605:
595:
594:
591:
590:
587:
586:
578:
577:
566:
560:
559:
556:
555:
547:
546:
543:
542:
540:
539:
535:
531:
527:
526:primary oocyte
523:
519:
515:
511:
507:
503:
499:
496:
495:
484:
481:
480:
478:
477:
473:
469:
465:
464:left ventricle
461:
457:
453:
449:
445:
441:
437:
434:
433:
421:
420:
412:
401:
395:
394:
391:RNA expression
383:
382:
379:
378:
370:
366:
365:
357:
354:
349:
343:
342:
333:
326:
320:
316:
315:
310:
304:
303:
295:
294:
282:
281:
278:
277:
269:
265:
264:
256:
253:
248:
242:
241:
232:
225:
219:
215:
214:
207:
201:
200:
192:
191:
179:
178:
135:
131:
130:
122:
114:
113:
109:
108:
105:
104:
101:
100:
82:
81:
73:
72:
61:
55:
54:
46:
45:
37:
36:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
6591:
6580:
6579:Immune system
6577:
6575:
6572:
6570:
6567:
6566:
6564:
6555:
6552:
6550:
6547:
6545:
6542:
6541:
6532:
6529:
6527:
6524:
6522:
6519:
6517:
6514:
6512:
6509:
6508:
6506:
6502:
6498:
6494:
6487:
6482:
6480:
6475:
6473:
6468:
6467:
6464:
6452:
6449:
6447:
6444:
6442:
6439:
6437:
6434:
6432:
6429:
6427:
6424:
6422:
6419:
6417:
6414:
6412:
6409:
6407:
6404:
6402:
6399:
6397:
6394:
6392:
6389:
6387:
6384:
6382:
6379:
6377:
6374:
6372:
6369:
6367:
6364:
6362:
6359:
6357:
6354:
6352:
6349:
6347:
6344:
6342:
6339:
6337:
6334:
6332:
6329:
6327:
6324:
6322:
6319:
6317:
6314:
6312:
6309:
6307:
6304:
6302:
6299:
6297:
6294:
6292:
6289:
6287:
6284:
6282:
6279:
6277:
6274:
6272:
6269:
6268:
6266:
6262:
6256:
6253:
6251:
6248:
6246:
6243:
6241:
6238:
6236:
6233:
6231:
6228:
6226:
6223:
6221:
6218:
6216:
6213:
6211:
6208:
6206:
6203:
6201:
6198:
6196:
6193:
6191:
6188:
6186:
6183:
6181:
6178:
6176:
6173:
6171:
6168:
6166:
6163:
6161:
6158:
6156:
6153:
6151:
6148:
6146:
6143:
6141:
6138:
6136:
6133:
6131:
6128:
6126:
6123:
6121:
6118:
6116:
6113:
6111:
6108:
6106:
6103:
6101:
6098:
6096:
6093:
6091:
6088:
6086:
6083:
6081:
6078:
6076:
6073:
6071:
6068:
6066:
6063:
6062:
6060:
6056:
6050:
6047:
6045:
6041:
6038:
6036:
6033:
6031:
6028:
6026:
6023:
6021:
6018:
6016:
6013:
6011:
6008:
6006:
6003:
6001:
5998:
5996:
5993:
5989:
5986:
5984:
5981:
5980:
5979:
5976:
5974:
5971:
5969:
5966:
5964:
5961:
5959:
5956:
5954:
5951:
5949:
5946:
5944:
5941:
5939:
5936:
5934:
5931:
5929:
5926:
5924:
5921:
5919:
5916:
5914:
5911:
5908:
5905:
5903:
5899:
5896:
5894:
5891:
5887:
5884:
5882:
5879:
5878:
5877:
5874:
5872:
5869:
5865:
5862:
5860:
5857:
5856:
5855:
5852:
5850:
5847:
5845:
5842:
5840:
5837:
5835:
5832:
5830:
5827:
5825:
5822:
5820:
5817:
5815:
5812:
5811:
5809:
5805:
5799:
5796:
5794:
5791:
5789:
5786:
5784:
5781:
5779:
5776:
5774:
5771:
5769:
5766:
5764:
5761:
5759:
5756:
5754:
5751:
5749:
5746:
5744:
5741:
5739:
5736:
5734:
5731:
5729:
5726:
5724:
5721:
5719:
5716:
5712:
5709:
5707:
5704:
5703:
5702:
5699:
5697:
5694:
5692:
5689:
5687:
5684:
5680:
5677:
5675:
5672:
5670:
5667:
5666:
5665:
5662:
5660:
5657:
5655:
5652:
5650:
5647:
5645:
5642:
5638:
5635:
5633:
5630:
5629:
5628:
5625:
5623:
5620:
5618:
5615:
5613:
5610:
5608:
5605:
5603:
5600:
5598:
5595:
5591:
5588:
5586:
5583:
5582:
5581:
5578:
5575:
5572:
5570:
5567:
5565:
5562:
5560:
5557:
5555:
5551:
5548:
5546:
5543:
5539:
5536:
5534:
5531:
5529:
5526:
5525:
5524:
5521:
5519:
5516:
5514:
5511:
5509:
5506:
5504:
5501:
5499:
5496:
5495:
5493:
5489:
5483:
5480:
5478:
5475:
5473:
5470:
5468:
5465:
5463:
5460:
5458:
5455:
5453:
5450:
5448:
5445:
5443:
5440:
5438:
5435:
5433:
5430:
5428:
5425:
5423:
5420:
5418:
5415:
5413:
5410:
5408:
5405:
5403:
5400:
5398:
5395:
5393:
5390:
5388:
5385:
5383:
5380:
5378:
5375:
5373:
5370:
5368:
5365:
5363:
5360:
5356:
5353:
5351:
5348:
5347:
5346:
5343:
5339:
5336:
5334:
5331:
5330:
5329:
5326:
5324:
5321:
5319:
5316:
5314:
5311:
5309:
5306:
5304:
5301:
5299:
5296:
5294:
5291:
5289:
5286:
5284:
5281:
5279:
5276:
5274:
5271:
5269:
5266:
5262:
5259:
5257:
5254:
5253:
5252:
5249:
5247:
5244:
5242:
5239:
5237:
5234:
5232:
5229:
5227:
5224:
5222:
5219:
5218:
5216:
5212:
5206:
5203:
5201:
5198:
5196:
5193:
5191:
5188:
5186:
5183:
5181:
5178:
5176:
5173:
5171:
5168:
5166:
5162:
5159:
5157:
5154:
5152:
5149:
5147:
5144:
5142:
5139:
5137:
5134:
5130:
5127:
5125:
5122:
5120:
5117:
5115:
5112:
5110:
5107:
5105:
5102:
5101:
5100:
5097:
5095:
5092:
5090:
5087:
5085:
5082:
5080:
5077:
5075:
5072:
5068:
5065:
5063:
5060:
5059:
5058:
5055:
5053:
5050:
5048:
5045:
5043:
5040:
5038:
5035:
5033:
5030:
5028:
5025:
5023:
5020:
5018:
5015:
5011:
5008:
5006:
5003:
5001:
4998:
4996:
4993:
4991:
4988:
4986:
4983:
4982:
4981:
4978:
4974:
4971:
4969:
4966:
4964:
4961:
4960:
4959:
4956:
4954:
4951:
4947:
4944:
4942:
4939:
4937:
4934:
4933:
4932:
4929:
4927:
4924:
4922:
4919:
4917:
4914:
4912:
4909:
4907:
4904:
4902:
4899:
4897:
4894:
4892:
4889:
4887:
4884:
4882:
4879:
4878:
4876:
4872:
4866:
4863:
4859:
4856:
4854:
4851:
4849:
4846:
4844:
4841:
4839:
4836:
4834:
4831:
4830:
4829:
4826:
4824:
4821:
4819:
4816:
4814:
4811:
4809:
4806:
4804:
4801:
4799:
4796:
4792:
4789:
4787:
4784:
4782:
4779:
4777:
4774:
4773:
4772:
4769:
4767:
4764:
4762:
4759:
4757:
4754:
4752:
4749:
4747:
4744:
4742:
4739:
4737:
4734:
4732:
4729:
4727:
4724:
4720:
4717:
4715:
4712:
4711:
4710:
4707:
4705:
4702:
4700:
4697:
4695:
4692:
4690:
4687:
4685:
4682:
4680:
4677:
4675:
4672:
4670:
4667:
4665:
4662:
4660:
4657:
4655:
4652:
4650:
4647:
4645:
4642:
4640:
4637:
4633:
4630:
4628:
4625:
4624:
4623:
4620:
4618:
4615:
4613:
4610:
4608:
4605:
4601:
4598:
4596:
4593:
4591:
4588:
4586:
4583:
4582:
4581:
4578:
4576:
4573:
4571:
4568:
4564:
4561:
4560:
4559:
4556:
4554:
4551:
4549:
4546:
4544:
4541:
4539:
4536:
4532:
4529:
4527:
4524:
4522:
4519:
4518:
4517:
4514:
4512:
4509:
4505:
4502:
4500:
4497:
4495:
4492:
4490:
4487:
4485:
4482:
4481:
4480:
4477:
4476:
4474:
4470:
4465:
4461:
4457:
4450:
4445:
4443:
4438:
4436:
4431:
4430:
4427:
4423:
4422:
4420:
4419:public domain
4416:
4407:
4403:
4402:
4397:
4393:
4389:
4386:
4382:
4379:
4378:
4374:
4367:
4363:
4359:
4355:
4349:
4345:
4341:
4336:
4331:
4327:
4323:
4319:
4315:
4311:
4306:
4302:
4298:
4294:
4290:
4287:(2): 109–16.
4286:
4282:
4277:
4273:
4269:
4265:
4261:
4258:(6): 1665–9.
4257:
4253:
4248:
4244:
4238:
4230:
4226:
4222:
4218:
4214:
4210:
4206:
4202:
4196:
4192:
4188:
4184:
4180:
4176:
4172:
4168:
4164:
4158:
4154:
4150:
4146:
4142:
4139:(6): 1770–3.
4138:
4134:
4128:
4124:
4120:
4116:
4112:
4108:
4104:
4098:
4094:
4090:
4086:
4082:
4078:
4074:
4068:
4064:
4060:
4056:
4052:
4048:
4044:
4039:
4035:
4031:
4027:
4023:
4019:
4015:
4010:
4006:
4002:
3997:
3992:
3988:
3984:
3980:
3976:
3972:
3967:
3963:
3959:
3954:
3949:
3945:
3941:
3937:
3932:
3928:
3924:
3920:
3916:
3912:
3908:
3904:
3900:
3894:
3890:
3886:
3882:
3878:
3875:(3): 215–20.
3874:
3870:
3865:
3861:
3857:
3852:
3847:
3843:
3839:
3835:
3830:
3826:
3822:
3818:
3814:
3810:
3806:
3801:
3800:
3795:
3787:
3783:
3778:
3773:
3769:
3765:
3761:
3757:
3753:
3746:
3743:
3738:
3734:
3729:
3724:
3719:
3714:
3710:
3706:
3702:
3698:
3694:
3687:
3684:
3679:
3675:
3670:
3665:
3661:
3657:
3653:
3649:
3645:
3638:
3635:
3630:
3626:
3622:
3618:
3614:
3610:
3606:
3602:
3594:
3592:
3588:
3583:
3579:
3574:
3569:
3564:
3559:
3555:
3551:
3550:Retrovirology
3547:
3540:
3538:
3534:
3529:
3525:
3520:
3515:
3510:
3505:
3501:
3497:
3493:
3485:
3482:
3477:
3473:
3468:
3463:
3459:
3455:
3451:
3447:
3443:
3436:
3433:
3428:
3422:
3419:
3414:
3410:
3405:
3400:
3396:
3392:
3388:
3381:
3378:
3367:
3363:
3357:
3354:
3349:
3345:
3339:
3336:
3329:
3324:
3318:
3317:
3314:
3310:
3305:
3300:
3296:
3292:
3288:
3284:
3280:
3272:
3269:
3264:
3260:
3255:
3250:
3246:
3242:
3239:(5): 275–87.
3238:
3234:
3230:
3223:
3221:
3219:
3217:
3213:
3208:
3204:
3199:
3194:
3190:
3186:
3182:
3175:
3173:
3169:
3164:
3160:
3156:
3152:
3148:
3144:
3140:
3136:
3132:
3128:
3121:
3118:
3113:
3109:
3104:
3099:
3094:
3089:
3085:
3081:
3077:
3073:
3069:
3062:
3060:
3056:
3051:
3047:
3042:
3037:
3033:
3029:
3026:(1): 98–106.
3025:
3021:
3017:
3010:
3007:
3002:
2998:
2993:
2988:
2984:
2980:
2976:
2972:
2968:
2960:
2957:
2952:
2948:
2943:
2938:
2934:
2930:
2926:
2922:
2918:
2914:
2910:
2902:
2899:
2894:
2890:
2886:
2882:
2878:
2874:
2867:
2864:
2859:
2855:
2851:
2847:
2843:
2839:
2832:
2829:
2824:
2820:
2815:
2810:
2805:
2800:
2796:
2792:
2788:
2781:
2778:
2771:
2767:
2762:
2757:
2753:
2749:
2745:
2741:
2737:
2730:
2727:
2722:
2718:
2713:
2708:
2704:
2700:
2697:(4): 265–76.
2696:
2692:
2688:
2681:
2678:
2673:
2669:
2664:
2659:
2655:
2651:
2647:
2643:
2639:
2631:
2628:
2623:
2619:
2614:
2609:
2605:
2601:
2597:
2590:
2587:
2582:
2578:
2574:
2570:
2566:
2562:
2558:
2554:
2550:
2546:
2539:
2536:
2531:
2527:
2522:
2517:
2514:(3): 634–43.
2513:
2509:
2505:
2498:
2495:
2490:
2486:
2482:
2478:
2474:
2470:
2466:
2462:
2454:
2451:
2446:
2442:
2437:
2432:
2429:(2): 141–51.
2428:
2424:
2420:
2413:
2410:
2405:
2401:
2396:
2391:
2388:(3): 1140–5.
2387:
2383:
2379:
2372:
2370:
2366:
2361:
2357:
2352:
2347:
2342:
2337:
2333:
2329:
2325:
2321:
2317:
2310:
2308:
2304:
2299:
2295:
2290:
2285:
2281:
2277:
2273:
2266:
2263:
2258:
2254:
2250:
2246:
2242:
2241:10.1038/85330
2238:
2234:
2230:
2222:
2220:
2216:
2211:
2207:
2202:
2197:
2193:
2189:
2185:
2181:
2177:
2169:
2167:
2165:
2161:
2156:
2152:
2148:
2144:
2141:(5): 765–72.
2140:
2136:
2135:
2127:
2124:
2119:
2115:
2110:
2105:
2101:
2097:
2093:
2089:
2085:
2078:
2075:
2070:
2066:
2062:
2058:
2053:
2048:
2044:
2040:
2037:(5): 739–45.
2036:
2032:
2028:
2021:
2018:
2013:
2009:
2004:
1999:
1994:
1989:
1985:
1981:
1977:
1970:
1968:
1964:
1959:
1955:
1950:
1945:
1941:
1937:
1933:
1929:
1925:
1918:
1916:
1914:
1910:
1898:
1894:
1887:
1884:
1879:
1875:
1871:
1867:
1863:
1859:
1855:
1851:
1847:
1843:
1836:
1833:
1828:
1824:
1819:
1814:
1810:
1806:
1802:
1798:
1794:
1787:
1784:
1779:
1775:
1771:
1767:
1763:
1759:
1752:
1750:
1748:
1746:
1744:
1742:
1740:
1738:
1736:
1732:
1727:
1721:
1719:
1717:
1713:
1708:
1704:
1700:
1696:
1692:
1688:
1681:
1678:
1673:
1669:
1663:
1660:
1655:
1651:
1645:
1642:
1638:
1634:
1629:
1627:
1625:
1621:
1617:
1613:
1608:
1606:
1604:
1600:
1594:
1592:
1583:
1580:
1576:
1568:
1563:
1561:
1559:
1555:
1551:
1547:
1543:
1539:
1535:
1530:
1528:
1524:
1522:
1518:
1517:Pembrolizumab
1514:
1512:
1508:
1504:
1500:
1495:
1491:
1483:
1481:
1479:
1475:
1471:
1466:
1462:
1459:
1454:
1452:
1448:
1442:
1440:
1434:
1432:
1428:
1423:
1421:
1417:
1413:
1409:
1408:immune system
1405:
1397:
1393:
1388:
1381:
1376:
1374:
1372:
1367:
1365:
1361:
1357:
1353:
1349:
1345:
1340:
1336:
1333:
1328:
1324:
1319:
1316:
1312:
1308:
1304:
1303:knockout mice
1296:
1294:
1292:
1288:
1284:
1280:
1276:
1272:
1268:
1264:
1260:
1256:
1253:PD-1 has two
1248:
1246:
1244:
1240:
1236:
1232:
1228:
1224:
1220:
1216:
1212:
1211:transmembrane
1208:
1204:
1200:
1196:
1192:
1188:
1180:
1178:
1175:
1171:
1167:
1159:
1157:
1155:
1151:
1147:
1143:
1138:
1136:
1132:
1130:
1126:
1122:
1118:
1114:
1109:
1107:
1103:
1099:
1098:immune system
1095:
1091:
1087:
1083:
1080:
1076:
1072:
1069:
1065:
1062:
1050:
1045:
1041:
1037:
1034:
1030:
1023:
1021:
1018:
1014:
1010:
1006:
1003:
999:
995:
988:
986:
980:
976:
973:
967:
965:
959:
955:
952:
948:
941:
939:
933:
929:
926:
920:
918:
912:
908:
905:
903:RefSeq (mRNA)
901:
894:
893:
888:
884:
881:
875:
874:
869:
865:
862:
860:
856:
849:
848:
843:
839:
836:
830:
829:
825:
820:
816:
813:
811:
807:
800:
799:
794:
790:
787:
781:
780:
775:
771:
768:
766:
762:
759:
756:
754:
751:
747:
744:
740:
736:
729:
725:
720:
714:
711:
709:
706:
704:
701:
699:
696:
694:
691:
689:
686:
684:
681:
679:
676:
674:
671:
669:
666:
665:
663:
660:
659:
653:
650:
648:
645:
643:
640:
638:
635:
634:
632:
629:
628:
622:
619:
617:
614:
613:
611:
608:
607:
604:
603:Gene ontology
600:
596:
584:
579:
575:
570:
567:
565:
561:
553:
548:
537:
533:
529:
525:
521:
517:
513:
509:
505:
501:
500:
497:
493:
488:
485:
475:
471:
467:
463:
459:
455:
452:right auricle
451:
447:
443:
439:
438:
435:
431:
426:
423:
422:
419:
417:
413:
411:
410:
406:
405:
402:
400:
396:
392:
388:
384:
376:
371:
367:
363:
358:
348:
344:
337:
330:
324:
317:
309:
305:
301:
296:
292:
287:
283:
275:
270:
266:
262:
257:
247:
243:
236:
229:
223:
216:
212:
206:
202:
198:
193:
189:
184:
180:
176:
172:
168:
164:
160:
156:
152:
148:
144:
140:
132:
127:
120:
115:
110:
99:
97:
93:
89:
83:
78:
75:
74:
70:
67:
60:
56:
51:
47:
43:
38:
33:
30:
19:
6174:
5977:
5897:
5875:
5853:
5700:
5663:
5626:
5579:
5549:
5522:
5344:
5250:
5098:
4827:
4579:
4412:
4411:
4399:
4357:
4353:
4317:
4313:
4284:
4280:
4255:
4251:
4237:cite journal
4207:(7): 510–6.
4204:
4200:
4169:(5): 393–8.
4166:
4162:
4136:
4132:
4109:(3): 770–5.
4106:
4102:
4079:(1): 327–8.
4076:
4072:
4049:(6): 492–7.
4046:
4042:
4020:(3): 672–7.
4017:
4013:
3978:
3974:
3946:(2): 711–8.
3943:
3939:
3905:(4): 666–9.
3902:
3898:
3872:
3868:
3841:
3837:
3808:
3804:
3759:
3755:
3745:
3700:
3696:
3686:
3651:
3647:
3637:
3607:(2): 135–7.
3604:
3600:
3553:
3549:
3499:
3495:
3484:
3452:(1): 81–90.
3449:
3445:
3435:
3421:
3394:
3390:
3380:
3369:. Retrieved
3365:
3356:
3347:
3338:
3327:
3286:
3282:
3271:
3236:
3232:
3188:
3184:
3130:
3126:
3120:
3075:
3071:
3023:
3019:
3009:
2974:
2970:
2959:
2916:
2912:
2901:
2879:(5): 430–9.
2876:
2872:
2866:
2841:
2837:
2831:
2794:
2790:
2780:
2743:
2739:
2729:
2694:
2690:
2680:
2648:(4): 452–9.
2645:
2641:
2630:
2603:
2599:
2589:
2548:
2544:
2538:
2511:
2507:
2497:
2464:
2460:
2453:
2426:
2422:
2412:
2385:
2381:
2323:
2319:
2279:
2275:
2265:
2235:(3): 261–8.
2232:
2228:
2183:
2179:
2138:
2132:
2126:
2091:
2087:
2077:
2034:
2030:
2020:
1983:
1979:
1931:
1927:
1900:. Retrieved
1896:
1886:
1848:(1): 45–59.
1845:
1841:
1835:
1800:
1796:
1786:
1761:
1757:
1693:(3): 704–6.
1690:
1686:
1680:
1671:
1662:
1653:
1644:
1589:
1572:
1546:atezolizumab
1531:
1525:
1515:
1501:, (Opdivo -
1496:
1493:
1478:Tasuku Honjo
1467:
1463:
1455:
1443:
1439:CD8+ T cells
1435:
1424:
1415:
1401:
1368:
1341:
1337:
1320:
1309:and dilated
1300:
1287:B16 melanoma
1252:
1184:
1170:Tasuku Honjo
1163:
1139:
1133:
1110:
1084:. PD-1 is a
1078:
1067:
1063:
1060:
1059:
982:
961:
935:
914:
890:
871:
845:
822:
796:
777:
757:
752:
522:cumulus cell
414:
407:
272:241,858,894
259:241,849,884
134:External IDs
85:
29:
3811:(1): 25–8.
3191:(1): 1–10.
2797:: 5023–39.
1538:pidilizumab
1527:Toripalimab
1243:macrophages
1191:amino acids
1125:lymph nodes
1111:PD-1 is an
444:granulocyte
373:93,980,278
360:93,966,027
112:Identifiers
6563:Categories
4462:(see also
3371:2019-08-25
2740:Oncotarget
1803:: 219–42.
1639:, May 2017
1618:, May 2017
1595:References
1542:BMS-936559
1536:) include
1447:ipilimumab
1344:thymocytes
1201:family of
440:lymph node
418:(ortholog)
352:1|1 D
155:HomoloGene
6504:receptors
2844:: 88–98.
2581:205210800
1507:Nivolumab
1499:nivolumab
1468:The 2018
1451:nivolumab
1348:apoptosis
1181:Structure
1166:apoptosis
1160:Discovery
1117:apoptosis
985:NP_032824
964:NP_005009
938:NM_008798
917:NM_005018
743:Orthologs
163:GeneCards
4456:Proteins
4366:16265694
4344:16227604
4301:16171790
4272:15934088
4229:33705026
4221:15352422
4183:15322919
4153:15188352
4123:15022318
4093:14730631
4063:14617032
4034:12893276
4005:12719480
3962:12517932
3927:20496046
3919:12402038
3889:12095712
3786:25073790
3737:26621719
3678:23552370
3629:20699898
3621:26779813
3582:25756928
3528:26741490
3476:22198819
3413:30805896
3313:22658127
3263:27079802
3207:23890059
3185:Immunity
3163:29830409
3155:24031011
3112:20160101
3050:26558876
3001:25409260
2951:25428504
2893:21074057
2858:26895815
2823:27574444
2770:28881780
2721:25797516
2672:20208540
2622:15837746
2573:16382236
2530:11857337
2489:11209085
2445:10485649
2423:Immunity
2404:14871849
2360:12218188
2298:12421930
2257:27659586
2249:11224527
2210:11015443
2118:21739608
2069:11384162
2061:17195077
2052:11030209
2012:28018338
1878:23843848
1870:21276005
1827:20636820
1778:29208439
1687:Genomics
1635:–
1614:–
1550:avelumab
1521:melanoma
1511:melanoma
1416:in vitro
1346:undergo
1297:Function
1033:Wikidata
722:Sources:
647:membrane
456:appendix
6264:301–350
6058:251–300
6010:CD240CE
5807:201–250
5491:151–200
5214:101–150
4406:PDBe-KB
4396:UniProt
4335:1265804
4191:8562917
3996:2193977
3860:9332365
3825:9141617
3777:4144739
3728:4679000
3705:Bibcode
3669:3684024
3573:4340294
3519:4704737
3467:3731769
3304:3544539
3254:5381938
3135:Bibcode
3127:Science
3103:2840093
3080:Bibcode
3041:4892769
2992:4315319
2942:4836193
2921:Bibcode
2814:4990391
2761:5581079
2712:4393798
2663:4229134
2553:Bibcode
2469:Bibcode
2461:Science
2328:Bibcode
2201:2193311
2155:8671665
2109:3191120
2003:5149523
1986:: 550.
1958:1396582
1850:Bibcode
1818:2919275
1707:7851902
1637:Ensembl
1616:Ensembl
1255:ligands
1249:Ligands
1239:B cells
1189:of 288
1146:ligands
1121:antigen
1094:B cells
1090:T cells
1075:protein
859:UniProt
810:Ensembl
749:Species
728:QuickGO
393:pattern
119:Aliases
6521:CTLA-4
6271:CD300A
6230:CDw293
6015:CD240D
5876:CD213a
5854:CDw210
5819:CD202b
5793:CDw199
5788:CDw198
5442:CD140b
4874:51–100
4401:Q15116
4387:(MeSH)
4364:
4342:
4332:
4299:
4270:
4227:
4219:
4189:
4181:
4151:
4121:
4091:
4061:
4032:
4003:
3993:
3960:
3925:
3917:
3887:
3858:
3823:
3784:
3774:
3735:
3725:
3676:
3666:
3627:
3619:
3580:
3570:
3556:: 14.
3526:
3516:
3474:
3464:
3411:
3311:
3301:
3261:
3251:
3205:
3161:
3153:
3110:
3100:
3048:
3038:
2999:
2989:
2949:
2939:
2913:Nature
2891:
2856:
2821:
2811:
2768:
2758:
2719:
2709:
2670:
2660:
2620:
2579:
2571:
2545:Nature
2528:
2487:
2443:
2402:
2358:
2351:129438
2348:
2296:
2255:
2247:
2208:
2198:
2153:
2116:
2106:
2067:
2059:
2049:
2010:
2000:
1956:
1949:556898
1946:
1902:24 Nov
1876:
1868:
1825:
1815:
1776:
1705:
1558:Pfizer
1412:cancer
1382:Cancer
1360:T cell
1279:GM-CSF
1241:, and
1203:T cell
1199:CTLA-4
1102:T cell
1064:(PD-1)
1019:search
1017:PubMed
892:Q02242
873:Q15116
765:Entrez
564:BioGPS
530:spleen
518:zygote
510:embryo
506:thymus
502:embryo
476:tonsil
448:spleen
251:2q37.3
151:104879
143:600244
6451:CD350
6446:CD349
6441:CD344
6436:CD340
6431:CD339
6426:CD338
6421:CD337
6416:CD336
6411:CD335
6406:CD334
6401:CD333
6396:CD332
6391:CD331
6386:CD329
6381:CD328
6376:CD327
6371:CD326
6366:CD325
6361:CD324
6356:CD322
6351:CD321
6346:CD320
6341:CD318
6336:CD317
6331:CD316
6326:CD315
6321:CD314
6316:CD312
6311:CD309
6306:CD307
6301:CD306
6296:CD305
6291:CD304
6286:CD303
6281:CD302
6276:CD301
6255:CD299
6250:CD298
6245:CD297
6240:CD295
6235:CD294
6225:CD292
6220:CD290
6215:CD289
6210:CD288
6205:CD286
6200:CD284
6195:CD283
6190:CD282
6185:CD281
6180:CD280
6175:CD279
6170:CD278
6165:CD276
6160:CD275
6155:CD274
6150:CD273
6145:CD272
6140:CD271
6135:CD269
6130:CD268
6125:CD267
6120:CD266
6115:CD265
6110:CD264
6105:CD263
6100:CD262
6095:CD261
6090:CD258
6085:CD257
6080:CD256
6075:CD254
6070:CD253
6065:CD252
6049:CD249
6044:CD248
6040:CD247
6035:CD246
6030:CD244
6025:CD243
6020:CD241
6005:CD239
6000:CD238
5995:CD236
5978:CD235
5973:CD234
5968:CD233
5963:CD230
5958:CD229
5953:CD228
5948:CD227
5943:CD226
5938:CD225
5933:CD224
5928:CD223
5923:CD222
5918:CD221
5913:CD220
5898:CD218
5893:CD217
5871:CD212
5849:CD209
5844:CD208
5839:CD207
5834:CD206
5829:CD205
5824:CD204
5814:CD201
5798:CD200
5783:CD197
5778:CD196
5773:CD195
5768:CD194
5763:CD193
5758:CD192
5753:CD191
5748:CD186
5743:CD185
5738:CD184
5733:CD183
5728:CD182
5723:CD181
5718:CD180
5701:CD179
5696:CD178
5691:CD177
5686:CD174
5664:CD172
5659:CD171
5654:CD170
5649:CD169
5644:CD168
5627:CD167
5622:CD166
5617:CD164
5612:CD163
5607:CD162
5602:CD161
5597:CD160
5580:CD159
5550:CD158
5545:CD157
5523:CD156
5518:CD155
5513:CD154
5508:CD153
5503:CD152
5498:CD151
5482:CD150
5477:CD148
5472:CD147
5467:CD146
5462:CD144
5457:CD143
5452:CD142
5447:CD141
5437:CD138
5432:CD137
5427:CD136
5422:CD135
5417:CD134
5412:CD133
5407:CD132
5402:CD131
5397:CD130
5392:CD129
5387:CD127
5382:CD126
5377:CD125
5372:CD124
5367:CD123
5362:CD122
5345:CD121
5328:CD120
5323:CD119
5318:CD118
5313:CD117
5308:CD116
5303:CD115
5298:CD114
5293:CD113
5288:CD112
5283:CD111
5278:CD110
5273:CD109
5268:CD108
5251:CD107
5246:CD106
5241:CD105
5236:CD104
5231:CD103
5226:CD102
5221:CD101
5205:CD100
4225:S2CID
4201:Lupus
4187:S2CID
3923:S2CID
3625:S2CID
3391:Drugs
3159:S2CID
2577:S2CID
2253:S2CID
2065:S2CID
1874:S2CID
1575:TIGIT
1458:PD-L1
1427:CTLA4
1291:IFN-γ
1263:PD-L2
1259:PD-L1
1235:CBL-b
1231:SHP-2
1227:SHP-1
1154:PD-L2
1150:PD-L1
1079:PDCD1
1068:CD279
798:18566
758:Mouse
753:Human
724:Amigo
538:ovary
534:blood
460:blood
416:Mouse
409:Human
356:Start
291:Mouse
255:Start
188:Human
167:PDCD1
126:PDCD1
35:PDCD1
18:CD279
6531:PD-1
6526:ICOS
6516:CD28
6511:BTLA
5200:CD99
5195:CD98
5190:CD97
5185:CD96
5180:CD95
5175:CD94
5170:CD93
5165:CD92
5161:CD91
5156:CD90
5151:CD89
5146:CD88
5141:CD87
5136:CD86
5099:CD85
5094:CD84
5089:CD83
5084:CD82
5079:CD81
5074:CD80
5057:CD79
5052:CD78
5047:CD74
5042:CD73
5037:CD72
5032:CD71
5027:CD70
5022:CD69
5017:CD68
4980:CD66
4958:CD64
4953:CD63
4931:CD62
4926:CD61
4921:CD59
4916:CD58
4911:CD57
4906:CD56
4901:CD55
4896:CD54
4891:CD53
4886:CD52
4881:CD51
4865:CD50
4828:CD49
4823:CD48
4818:CD47
4813:CD46
4808:CD45
4803:CD44
4798:CD43
4771:CD42
4766:CD41
4761:CD40
4756:CD39
4751:CD38
4746:CD37
4741:CD36
4736:CD35
4731:CD34
4726:CD33
4709:CD32
4704:CD31
4699:CD30
4694:CD29
4689:CD28
4684:CD27
4679:CD26
4674:CD25
4669:CD24
4664:CD23
4659:CD22
4654:CD21
4649:CD20
4644:CD19
4639:CD18
4622:CD16
4617:CD15
4612:CD14
4607:CD13
4580:CD11
4575:CD10
4472:1–50
4394:for
4362:PMID
4340:PMID
4297:PMID
4268:PMID
4243:link
4217:PMID
4179:PMID
4149:PMID
4119:PMID
4089:PMID
4059:PMID
4030:PMID
4001:PMID
3958:PMID
3915:PMID
3885:PMID
3856:PMID
3838:Gene
3821:PMID
3782:PMID
3733:PMID
3674:PMID
3617:PMID
3578:PMID
3524:PMID
3472:PMID
3409:PMID
3309:PMID
3259:PMID
3203:PMID
3151:PMID
3108:PMID
3046:PMID
2997:PMID
2947:PMID
2889:PMID
2854:PMID
2819:PMID
2766:PMID
2717:PMID
2668:PMID
2618:PMID
2569:PMID
2526:PMID
2485:PMID
2441:PMID
2400:PMID
2356:PMID
2294:PMID
2245:PMID
2206:PMID
2151:PMID
2114:PMID
2057:PMID
2008:PMID
1954:PMID
1904:2014
1866:PMID
1846:1217
1823:PMID
1774:PMID
1703:PMID
1556:and
1476:and
1332:LCMV
1325:and
1283:mRNA
1277:and
1261:and
1229:and
1195:CD28
1152:and
1092:and
1082:gene
779:5133
399:Bgee
347:Band
308:Chr.
246:Band
205:Chr.
159:3681
139:OMIM
96:4ZQK
92:3RRQ
88:2M2D
69:RCSB
66:PDBe
4570:CD9
4558:CD8
4553:CD7
4548:CD6
4543:CD5
4538:CD4
4516:CD3
4511:CD2
4484:a-c
4479:CD1
4392:PDB
4330:PMC
4322:doi
4289:doi
4285:235
4260:doi
4209:doi
4171:doi
4167:115
4141:doi
4111:doi
4081:doi
4051:doi
4022:doi
4018:307
3991:PMC
3983:doi
3979:197
3948:doi
3944:170
3907:doi
3877:doi
3846:doi
3842:197
3813:doi
3809:232
3772:PMC
3764:doi
3760:211
3723:PMC
3713:doi
3701:112
3664:PMC
3656:doi
3609:doi
3568:PMC
3558:doi
3514:PMC
3504:doi
3462:PMC
3454:doi
3399:doi
3299:PMC
3291:doi
3287:366
3249:PMC
3241:doi
3193:doi
3143:doi
3131:341
3098:PMC
3088:doi
3076:107
3036:PMC
3028:doi
2987:PMC
2979:doi
2975:371
2937:PMC
2929:doi
2917:515
2881:doi
2846:doi
2842:100
2809:PMC
2799:doi
2756:PMC
2748:doi
2707:PMC
2699:doi
2658:PMC
2650:doi
2608:doi
2561:doi
2549:439
2516:doi
2477:doi
2465:291
2431:doi
2390:doi
2346:PMC
2336:doi
2284:doi
2280:169
2237:doi
2196:PMC
2188:doi
2184:192
2143:doi
2104:PMC
2096:doi
2047:PMC
2039:doi
1998:PMC
1988:doi
1944:PMC
1936:doi
1858:doi
1813:PMC
1805:doi
1801:236
1766:doi
1695:doi
1579:HIV
1569:HIV
1327:CD8
1323:CD4
1315:CD3
1275:LPS
1223:TCR
1207:IgV
1088:on
1066:, (
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268:End
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