301:
pathways within the bone marrow are antagonistic and dependent on the relative expression of IRF8 and c/EBP transcription factors (and hence there is not a direct precursor-progeny link between these two myeloid cell types), this seems not to be the case for MDSCs. Monocytic MDSCs seem to be precursors of granulocytic subsets demonstrated both in vitro and in vivo. This differentiation process is accelerated upon tumor infiltration and possibly driven by the hypoxic tumor microenvironment.
315:
caused T and NK-cell dysfunction along with downregulation of the TCR z chain (CD247). The immunosuppressive milieu directly affects CD247, which is crucial in initiating immune responses. MDSCs, acting through membrane-bound TGF-b1, inhibit NK cells in tumor-bearing hosts due to the activity of TGF-b1 on MDSCs. Therefore, MDSCs constitutively suppress hepatic NK cells in tumor-bearing hosts through TGF-b1 on MDSCs.
22:
178:
to peripheral tissues (or tumors), where they differentiate into mature macrophages, dendritic cells, and neutrophils without suppressive phenotypes under homeostatic conditions, but become polarized when exposed to pro-inflammatory compounds, chemokines, and cytokines. In the tumor microenvironment,
105:
to regulate their functions. Tumors with high levels of infiltration by MDSCs have been associated with poor patient outcome and resistance to therapies. MDSCs can also be detected in the blood. In patients with breast cancer, levels of MDSC in blood are about 10-fold higher than normal. The size of
340:
treatment of bone marrow-derived MDSCs limits DC formation and improves MDSC suppressive action. MDSCs have been shown to reduce the effectiveness of DC vaccinations. MDSC frequency has no effect on DC production or survivability, but it does cause a dose-dependent reduction in DC maturation. High
345:
CHLA-DR/low cell frequencies can stifle DC maturation and decrease DC function, both of which are critical for vaccination effectiveness. As a result, the balance between MDSCs and DCs might be crucial in tumor and infection treatment. Thus, the balance between MDSCs and DCs may play an important
314:
The depletion of MDSCs from mice with liver cancer significantly increases natural killer (NK) cell cytotoxicity, NKG2D expression, and IFNg (IFNg) production and induces NK cell energy. MDSC depletion restored the function of impaired hepatic NK cells. An MDSC derived from chronic inflammation
199:. There are subpopulations of MDSC that have some common suppressive characteristics but also have their own unique features; different subpopulations can be found in different areas of the same tissue or tumor. Tumor-infiltrating MDSCs develop in response to environmental factors, upregulating
323:
A number of studies have reported MDSC regulation of B-cell responses to activators and mitogens that are not MHC-regulated, as well as antigen-specific T cell responses. An infection with the LP-BM5 retrovirus can cause acquired immune deficiency in mice, which causes highly immunosuppressive
300:
Murine MDSCs show two distinct phenotypes which discriminate them into either monocytic MDSCs or granulocytic MDSCs. The relationship between these two subtypes remains controversial, as they closely resemble monocytes and neutrophils respectively. While monocyte and neutrophil differentiation
462:
There is promising evidence for inhibiting
Galectin-3 as a therapeutic target to reduce MDSCs. In a Phase 1b clinical trial of GR-MD-02 developed by Galectin Therapeutics, investigators observed a significant decrease in the frequency of suppressive myeloid-derived suppressor cells following
439:
belonging to different classes have been reported to inhibit MDSC. Although this effect may well be secondary to inhibition of hematopoietic progenitors, there may be grounds for search of selectivity based on long-known differential effects of these agents on immunocompetent cells and
1745:
444:. In 2015, MDSCs were compared to immunogenic myeloid cells highlighting a group of core signaling pathways that control pro-carcinogenic MDSC functions. Many of these pathways are known targets of chemotherapy drugs with strong anti-cancer properties.
126:
MDSCs are formed from bone marrow precursors when myelopoietic processes are interrupted, caused by several illnesses. Cancer patients' growing tumors produce cytokines and other substances that affect MDSC development. Tumor cell lines overexpress
89:. MDSCs differ from other myeloid cell types in that they have immunosuppressive activities, as opposed to immune-stimulatory properties. Similar to other myeloid cells, MDSCs interact with immune cell types such as
746:
Safarzadeh E, Hashemzadeh S, Duijf PH, Mansoori B, Khaze V, Mohammadi A, et al. (April 2019). "Circulating myeloid-derived suppressor cells: An independent prognostic factor in patients with breast cancer".
422:
induced cytokine inflammation. This vaccination inducement appears to be neither permanent nor chronic. Despite MDSC's being immunosuppressive in certain instances, the MMR vaccine itself is immunostimulatory.
280:
have been implicated in the development and regulation of MDSC. The myeloid-differentiation cytokine GM-CSF is a key factor in MDSC production from bone marrow, and it has been shown that the c/EBPβ
1650:
Wang T, Chu Z, Lin H, Jiang J, Zhou X, Liang X (June 2014). "Galectin-3 contributes to cisplatin-induced myeloid derived suppressor cells (MDSCs) recruitment in Lewis lung cancer-bearing mice".
179:
they suppress the anti-tumor immune response. The presence of MDSCs has been associated with progression of colon cancer, tumor angiogenesis, and metastases. In addition to producing
240:
MDSCs derive from bone marrow precursors usually as the result of a perturbed myeloipoiesis caused by different pathologies. In cancer patients, growing tumors secrete a variety of
1244:"Faculty Opinions recommendation of Tumor necrosis factor-α blocks differentiation and enhances the suppressive activity of immature myeloid cells during chronic inflammation"
333:
792:"Targeting the Myeloid-Derived Suppressor Cell Compartment for Inducing Responsiveness to Immune Checkpoint Blockade Is Best Limited to Specific Subtypes of Gastric Cancers"
40:
1097:"A highly efficient tumor-infiltrating MDSC differentiation system for discovery of anti-neoplastic targets, which circumvents the need for tumor establishment in mice"
118:
therapy. Studies are needed to determine whether MDSCs are a population of immature myeloid cells that have stopped differentiation or a distinct myeloid lineage.
1290:"Myeloid-derived suppressor cells in murine retrovirus-induced AIDS inhibit T- and B-cell responses in vitro that are used to define the immunodeficiency"
615:"Immunology in the clinic review series; focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment"
159:
have been associated with the formation and regulation of MDSCs. GM-CSF promotes synthesis of MDSCs from bone marrow, and the transcription factor
662:
Galdiero MR, Bonavita E, Barajon I, Garlanda C, Mantovani A, Jaillon S (November 2013). "Tumor associated macrophages and neutrophils in cancer".
926:"Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade"
332:
Immune responses against tumors and infections are regulated by myeloid-derived suppressor cells and dendritic cells (DCs). The combination of
901:
132:
264:
allow the in vitro generation of MDSC that retain their suppressive function in vivo. In addition to CSF, other cytokines such as IL-6,
1538:
Gato-Cañas M, Martinez de
Morentin X, Blanco-Luquin I, Fernandez-Irigoyen J, Zudaire I, Liechtenstein T, et al. (September 2015).
152:
1746:"Positive Preliminary Results from Phase 1b Clinical Trial of GR-MD-02 and KEYTRUDA® in Advanced Melanoma and Expansion of the Trial"
204:
58:
418:, inhibiting septic inflammation and mortality that is broadly applicable not only to measles, mumps, and rubella, but extends to
1499:"Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species"
160:
1586:
1045:"Myeloid cells obtained from the blood but not from the tumor can suppress T-cell proliferation in patients with melanoma"
1016:
Gabrilovich D (2013-01-01). "Abstract IA7: Regulation of myeloid-derived suppressor cells in tumor micro-environment".
493:
or granulocytic MDSC (PMN-MDSC). M-MDSC are similar to monocytes found in blood, while PMN-MDSC are physically akin to
981:
Poschke I, Kiessling R (September 2012). "On the armament and appearances of human myeloid-derived suppressor cells".
394:. Inhibition can be caused by different mechanisms. It is primarily attributed to the effects of the metabolism of
249:
882:
Fan D, Raychoudhury S, Ai W (2020-05-13), "KLF4-Mediated
Plasticity of Myeloid-Derived Suppressor Cells (MDSCs)",
110:, highlighting the importance of this cell type for human pathophysiology. A high level of MDSC infiltrate in the
477:
128:
1095:
Liechtenstein T, Perez-Janices N, Gato M, Caliendo F, Kochan G, Blanco-Luquin I, et al. (September 2014).
143:, which promote development of MDSCs that have immune suppressive function in vivo. Other cytokines, including
284:
plays a key role in the generation of in vitro bone marrow-derived and in vivo tumor-induced MDSC. Moreover,
1146:"Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer"
436:
399:
1339:"Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development"
114:(TME) correlates with shorter survival times of patients with solid tumors and could mediate resistance to
111:
1775:
1261:
188:
106:
the myeloid suppressor compartment is considered to be an important factor in the success or failure of
1603:"Therapeutic prospects of targeting myeloid-derived suppressor cells and immune checkpoints in cancer"
85:
MDSCs expand under pathologic conditions such as chronic infection and cancer, as a result of altered
937:
432:
281:
220:
115:
107:
924:
Ouzounova M, Lee E, Piranlioglu R, El
Andaloussi A, Kolhe R, Demirci MF, et al. (April 2017).
102:
1675:
1632:
1425:
1368:
907:
772:
482:
415:
390:. Suppressor activity of MDSC is determined by their ability to inhibit the effector function of
355:
324:
CD11bCGr-1CLy6CC MDSCs. These cells suppress T and B cells by signaling via nitric oxide (NO).
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547:
490:
224:
833:"Turn Back the TIMe: Targeting Tumor Infiltrating Myeloid Cells to Revert Cancer Progression"
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156:
452:
1274:
383:
1144:
Youn JI, Kumar V, Collazo M, Nefedova Y, Condamine T, Cheng P, et al. (March 2013).
1043:
Gros A, Turcotte S, Wunderlich JR, Ahmadzadeh M, Dudley ME, Rosenberg SA (October 2012).
1412:
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941:
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515:
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265:
94:
86:
1769:
1448:"Myeloid-Derived Suppressor Cells: Facilitators of Cancer and Obesity-Induced Cancer"
1195:"Phenotype, development, and biological function of myeloid-derived suppressor cells"
1029:
911:
630:
370:
and other non-immune means. MDSC activity was originally described as suppressors of
367:
277:
261:
180:
1679:
1429:
1372:
776:
1636:
1386:
Poschke I, Mao Y, Adamson L, Salazar-Onfray F, Masucci G, Kiessling R (June 2012).
485:
et al. Publications in 2008 established that there are two subpopulations of MDSC:
375:
1711:
1694:
1252:
1243:
1210:
1060:
574:"The growing diversity and spectrum of action of myeloid-derived suppressor cells"
808:
791:
1695:"Re-wiring regulatory cell networks in immunity by galectin-glycan interactions"
1388:"Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines"
675:
486:
441:
411:
391:
387:
212:
175:
1515:
1498:
994:
252:(e.g. G-CSF and GM-CSF) have long been used in vivo models of MDSC generation.
1663:
1403:
532:
494:
395:
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maintenance and progression. MDSCs also obstruct therapies that seek to treat
245:
244:
and other molecules which are key signals involved in the generation of MDSC.
216:
98:
1555:
1540:"A core of kinase-regulated interactomes defines the neoplastic MDSC lineage"
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892:
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551:
148:
1355:
1338:
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573:
398:. Another important factor influencing the activity of MDSC is oppressive
1693:
Blidner AG, Méndez-Huergo SP, Cagnoni AJ, Rabinovich GA (November 2015).
1305:
419:
379:
196:
192:
144:
140:
949:
831:
Awad RM, De
Vlaeminck Y, Maebe J, Goyvaerts C, Breckpot K (2018-08-31).
82:
lineage (a family of cells that originate from bone marrow stem cells).
1619:
1602:
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from the environment and is necessary for mitochondrial biosynthesis),
79:
1721:
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448:
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253:
136:
90:
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714:
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responses. The spectrum of action of MDSC activity also encompasses
410:
MDSCs can also play a positive regulatory role. It is stated that
1497:
Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI (January 2004).
359:
285:
257:
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164:
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289:
273:
269:
200:
168:
1337:
Greifenberg V, Ribechini E, Rössner S, Lutz MB (October 2009).
15:
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regulates development of MDSCs in bone marrow and in tumors.
697:
Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (March 2012).
292:
has been suggested to counterbalance MDSC-inducing signals.
451:
approved drugs developed to target MDSCs but experimental
516:"c-Rel is a myeloid checkpoint for cancer immunotherapy"
36:
1193:
Zhao Y, Wu T, Shao S, Shi B, Zhao Y (February 2016).
78:) are a heterogeneous group of immune cells from the
1588:
INmune Bio
Initiates Phase I Clinical Trial Of INB03
699:"Coordinated regulation of myeloid cells by tumours"
187:, MDSCs secrete immune-regulatory cytokines such as
31:
may be too technical for most readers to understand
1090:
1088:
475:originated in a 2007 journal article published in
1024:. American Association for Cancer Research: IA7.
227:that can inhibit the anti-tumor immune response.
288:promotes MDSC differentiation and expansion and
1288:Green KA, Cook WJ, Green WR (February 2013).
8:
167:also promotes development of MDSCs, whereas
790:Kodach LL, Peppelenbosch MP (August 2021).
463:treatment in responding melanoma patients.
1441:
1439:
1744:Galectin Therapeutics Inc. (2018-09-20).
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613:Allavena P, Mantovani A (February 2012).
589:
567:
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223:). Tumor-infiltrating MDSCs also secrete
174:MDSCs migrate as immature cells from the
59:Learn how and when to remove this message
43:, without removing the technical details.
171:could counteract MDSC-inducing signals.
1465:10.1146/annurev-cancerbio-042120-105240
506:
1270:
1259:
414:stimulates MDSC populations in people
431:In addition to host-derived factors,
346:role in tumor and infection therapy.
41:make it understandable to non-experts
7:
619:Clinical and Experimental Immunology
435:also have profound impact on MDSC.
211:(an immune checkpoint protein) and
1601:Toor SM, Elkord E (October 2018).
1446:Ostrand-Rosenberg S (2021-03-04).
14:
1392:Cancer Immunology, Immunotherapy
1030:10.1158/1538-7445.tumimm2012-ia7
631:10.1111/j.1365-2249.2011.04515.x
514:Li T, Li X, Chen YH (May 2020).
72:Myeloid-derived suppressor cells
20:
1452:Annual Review of Cancer Biology
473:myeloid-derived suppressor cell
1343:European Journal of Immunology
749:Journal of Cellular Physiology
578:European Journal of Immunology
1:
1712:10.1016/j.febslet.2015.08.037
1253:10.3410/f.718002932.793475483
1211:10.1080/2162402x.2015.1004983
1061:10.1158/1078-0432.CCR-12-1108
572:Mantovani A (December 2010).
809:10.1053/j.gastro.2021.03.047
447:As of May 2018 there are no
1607:Immunology and Cell Biology
676:10.1016/j.imbio.2013.06.003
1792:
1516:10.4049/jimmunol.172.2.989
995:10.1016/j.clim.2012.06.003
884:Cells of the Immune System
703:Nature Reviews. Immunology
250:colony stimulating factors
129:colony-stimulating factors
1664:10.1007/s11033-014-3276-5
1652:Molecular Biology Reports
1404:10.1007/s00262-011-1143-y
1242:Engwerda C (2013-04-26).
533:10.1038/s43018-020-0061-3
406:Effect of MMR vaccination
1556:10.18632/oncotarget.4746
1113:10.18632/oncotarget.2279
1049:Clinical Cancer Research
893:10.5772/intechopen.89151
850:10.3389/fimmu.2018.01977
1750:GlobeNewswire News Room
837:Frontiers in Immunology
437:Chemotherapeutic agents
1269:Cite journal requires
1018:Tumor Microenvironment
112:tumor microenvironment
1503:Journal of Immunology
1356:10.1002/eji.200939486
930:Nature Communications
591:10.1002/eji.201041170
248:lines overexpressing
1306:10.1128/jvi.01547-12
433:pharmacologic agents
310:Natural killer cells
282:transcription factor
231:MDSC differentiation
221:fatty acid oxidation
116:checkpoint inhibitor
108:cancer immunotherapy
103:natural killer cells
1294:Journal of Virology
983:Clinical Immunology
950:10.1038/ncomms14979
942:2017NatCo...814979O
374:, in particular of
358:and play a role in
1620:10.1111/imcb.12054
489:MDSC (M-MDSC) and
455:has entered early
416:taking the vaccine
356:immune suppressive
1349:(10): 2865–2876.
1150:Nature Immunology
903:978-1-78985-583-8
761:10.1002/jcp.26896
491:polymorphonuclear
350:Activity/function
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487:mononuclear
483:Gabrilovich
442:macrophages
412:MMR vaccine
392:lymphocytes
388:macrophages
376:CD8+ T-cell
176:bone marrow
99:macrophages
1755:2019-03-14
1722:11336/7740
1544:Oncotarget
1101:Oncotarget
802:(2): 727.
501:References
396:L-arginine
354:MDSCs are
246:Tumor cell
217:fatty acid
215:(promotes
1484:2472-3428
912:209582254
471:The term
305:Phenotype
242:cytokines
236:In humans
122:Formation
1770:Category
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1629:29635843
1590:May 2018
1574:26320174
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380:NK cells
225:exosomes
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1565:4694980
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938:Bibcode
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724:3587148
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372:T cells
319:B cells
296:In mice
91:T cells
80:myeloid
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1676:S2CID
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773:S2CID
453:INB03
360:tumor
286:STAT3
266:IL-10
258:G-CSF
209:PDL-1
165:STAT3
161:c/EBP
133:G-CSF
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338:IFNg
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