Abstract
Myeloid-derived suppressor cells (MDSCs) are immature bone marrow–derived suppressive cells that are an important component of the pathological immune response associated with cancer. Expansion of MDSCs has been linked to poor disease outcome and therapeutic resistance in patients with various malignancies, making these cells potential targets for next-generation treatment strategies. MDSCs are classified into monocytic (M-MDSC) and polymorphonuclear/granulocytic (PMN-MDSC) subtypes that undertake distinct and numerous roles in the tumor microenvironment or systemically to drive disease progression. In this chapter, we will discuss how MDSC subsets contribute to the growth of primary tumors and induce metastatic spread by suppressing the antitumor immune response, supporting cancer stem cell (CSC)/epithelial-to-mesenchymal transition (EMT) phenotypes and promoting angiogenesis. We will also summarize the signaling networks involved in the crosstalk between cancer cells and MDSCs that could represent putative immunotherapy targets.
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Abbreviations
- Arg1:
-
arginase 1
- CCA:
-
cholangiocarcinoma
- CMP:
-
common myeloid progenitor
- COX2:
-
cyclooxygenase 2
- CSC:
-
cancer stem cell
- CTC:
-
circulating tumor cell
- DC:
-
dendritic cell
- EMT:
-
epithelial-to-mesenchymal transition
- ER:
-
endoplasmic reticulum
- FAO:
-
fatty acid oxidation
- GBM:
-
glioblastoma
- G-CSF:
-
granulocyte colony stimulating factor
- GM-CSF:
-
granulocyte-macrophage colony–stimulating factor
- GMP :
-
granulocyte-macrophage progenitor
- GP:
-
granulocyte progenitor
- HCC:
-
hepatocellular carcinoma
- HIF-1a:
-
hypoxia-inducible factor 1α
- HNSCC:
-
head and neck squamous cell carcinoma
- HSC:
-
hematopoietic stem cell
- IDO:
-
indole amine 2,3 dioxygenase
- IFN:
-
interferon
- IL:
-
interleukin
- IRF8:
-
interferon regulatory factor-8
- L-Arg:
-
L-arginine
- M-CSF:
-
macrophage colony–stimulating factor
- MDP:
-
macrophage and DC progenitor
- MDSC:
-
myeloid-derived suppressor cell
- MIF:
-
macrophage migration–inhibitory factor
- MLPG:
-
monocyte-like precursor of granulocyte
- M-MDSC:
-
monocytic MDSC
- MMP:
-
matrix metalloproteinase
- MPO:
-
myeloperoxidase
- NET:
-
neuroendocrine tumor
- NF-κB :
-
nuclear factor kappa B
- NO:
-
nitric oxide
- NOS:
-
NO synthase
- PD-L1:
-
programmed death-ligand 1
- PGE2:
-
prostaglandin E2
- PMN-MDSC :
-
polymorphonuclear MDSC
- PNT:
-
peroxynitrite
- RCC:
-
renal cell carcinoma
- ROS:
-
reactive oxygen species
- STAT:
-
signal transducer and activator protein
- TAM:
-
tumor-associated macrophage
- TGF:
-
transforming growth factor
- TLR:
-
Toll-like receptor
- TNF:
-
tumor necrosis factor
- TNFR:
-
TNF receptor
- VEGF:
-
vascular endothelial growth factor
References
Ai L, Mu S, Sun C et al (2019) Myeloid-derived suppressor cells endow stem-like qualities to multiple myeloma cells by inducing piRNA-823 expression and DNMT3B activation. Mol Cancer 18(1):88. https://doi.org/10.1186/s12943-019-1011-5
Alban TJ, Alvarado AG, Sorensen MD et al (2018) Global immune fingerprinting in glioblastoma patient peripheral blood reveals immune-suppression signatures associated with prognosis. Insight 3(21). https://doi.org/10.1172/jci.insight.122264
Alban TJ, Bayik D, Otvos B et al (2020) Glioblastoma myeloid-derived suppressor cell subsets express differential macrophage migration inhibitory factor receptor profiles that can be targeted to reduce immune suppression. Front Immunol 11:1191. https://doi.org/10.3389/fimmu.2020.01191
Al-Khami AA, Zheng L, Del Valle L et al (2017) Exogenous lipid uptake induces metabolic and functional reprogramming of tumor-associated myeloid-derived suppressor cells. Onco Targets Ther 6(10):e1344804. https://doi.org/10.1080/2162402X.2017.1344804
Almand B, Clark JI, Nikitina E et al (2001) Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166(1):678–689. https://doi.org/10.4049/jimmunol.166.1.678
Almand B, Resser JR, Lindman B et al (2000) Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 6(5):1755–1766
Alshetaiwi H, Pervolarakis N, McIntyre LL et al (2020) Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics. Sci Immunol 5(44). https://doi.org/10.1126/sciimmunol.aay6017
Arihara F, Mizukoshi E, Kitahara M et al (2013) Increase in CD14+HLA-DR −/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis. Cancer Immunol Immunother 62(8):1421–1430. https://doi.org/10.1007/s00262-013-1447-1
Baumann T, Dunkel A, Schmid C et al (2020) Regulatory myeloid cells paralyze T cells through cell-cell transfer of the metabolite methylglyoxal. Nat Immunol 21(5):555–566. https://doi.org/10.1038/s41590-020-0666-9
Bayik D, Lauko AJ, Roversi GA et al (2020a) Hepatobiliary malignancies have distinct peripheral myeloid-derived suppressor cell signatures and tumor myeloid cell profiles. Sci Rep 10(1):18848. https://doi.org/10.1038/s41598-020-75881-1
Bayik D, Tross D, Klinman DM (2018) Factors influencing the differentiation of human Monocytic myeloid-derived suppressor cells into inflammatory macrophages. Front Immunol 9:608. https://doi.org/10.3389/fimmu.2018.00608
Bayik D, Zhou Y, Park C et al (2020b) Myeloid-derived suppressor cell subsets drive glioblastoma growth in a sex-specific manner. Cancer Discov 10(8):1210–1225. https://doi.org/10.1158/2159-8290.CD-19-1355
Becker AM, Michael DG, Satpathy AT et al (2012) IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors. Blood 119(9):2003–2012. https://doi.org/10.1182/blood-2011-06-364976
Beury DW, Parker KH, Nyandjo M et al (2014) Cross-talk among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors. J Leukoc Biol 96(6):1109–1118. https://doi.org/10.1189/jlb.3A0414-210R
Binsfeld M, Muller J, Lamour V et al (2016) Granulocytic myeloid-derived suppressor cells promote angiogenesis in the context of multiple myeloma. Oncotarget 7(25):37931–37943. https://doi.org/10.18632/oncotarget.9270
Bronte V, Brandau S, Chen SH et al (2016) Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun 7:12150. https://doi.org/10.1038/ncomms12150
Bunt SK, Sinha P, Clements VK et al (2006) Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression. J Immunol 176(1):284–290. https://doi.org/10.4049/jimmunol.176.1.284
Bunt SK, Yang L, Sinha P et al (2007) Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res 67(20):10019–10026. https://doi.org/10.1158/0008-5472.CAN-07-2354
Cassetta L, Bruderek K, Skrzeczynska-Moncznik J et al (2020) Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation. J Immunother Cancer 8(2). https://doi.org/10.1136/jitc-2020-001223
Chai E, Zhang L, Li C (2019) LOX-1+ PMN-MDSC enhances immune suppression which promotes glioblastoma multiforme progression. Cancer Manag Res 11:7307–7315. https://doi.org/10.2147/CMAR.S210545
Chang AL, Miska J, Wainwright DA et al (2016) CCL2 produced by the glioma microenvironment is essential for the recruitment of regulatory T cells and myeloid-derived suppressor cells. Cancer Res 76(19):5671–5682. https://doi.org/10.1158/0008-5472.CAN-16-0144
Chen MF, Kuan FC, Yen TC et al (2014) IL-6-stimulated CD11b+ CD14+ HLA-DR- myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus. Oncotarget 5(18):8716–8728. https://doi.org/10.18632/oncotarget.2368
Cheng P, Corzo CA, Luetteke N et al (2008) Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J Exp Med 205(10):2235–2249. https://doi.org/10.1084/jem.20080132
Chun E, Lavoie S, Michaud M et al (2015) CCL2 promotes colorectal carcinogenesis by enhancing Polymorphonuclear myeloid-derived suppressor cell population and function. Cell Rep 12(2):244–257. https://doi.org/10.1016/j.celrep.2015.06.024
Cimen Bozkus C, Elzey BD, Crist SA et al (2015) Expression of cationic amino acid transporter 2 is required for myeloid-derived suppressor cell-mediated control of T cell immunity. J Immunol 195(11):5237–5250. https://doi.org/10.4049/jimmunol.1500959
Clavijo PE, Moore EC, Chen J et al (2017) Resistance to CTLA-4 checkpoint inhibition reversed through selective elimination of granulocytic myeloid cells. Oncotarget 8(34):55804–55820. https://doi.org/10.18632/oncotarget.18437
Condamine T, Dominguez GA, Youn JI et al (2016) Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci Immunol 1(2). https://doi.org/10.1126/sciimmunol.aaf8943
Condamine T, Kumar V, Ramachandran IR et al (2014) ER stress regulates myeloid-derived suppressor cell fate through TRAIL-R-mediated apoptosis. J Clin Invest 124(6):2626–2639. https://doi.org/10.1172/JCI74056
Condamine T, Mastio J, Gabrilovich DI (2015) Transcriptional regulation of myeloid-derived suppressor cells. J Leukoc Biol 98(6):913–922. https://doi.org/10.1189/jlb.4RI0515-204R
Corzo CA, Condamine T, Lu L et al (2010) HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med 207(11):2439–2453. https://doi.org/10.1084/jem.20100587
Cui TX, Kryczek I, Zhao L et al (2013) Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity 39(3):611–621. https://doi.org/10.1016/j.immuni.2013.08.025
Davis RJ, Moore EC, Clavijo PE et al (2017) Anti-PD-L1 efficacy can be enhanced by inhibition of myeloid-derived suppressor cells with a selective inhibitor of PI3Kdelta/gamma. Cancer Res 77(10):2607–2619. https://doi.org/10.1158/0008-5472.CAN-16-2534
Diaz-Montero CM, Salem ML, Nishimura MI et al (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58(1):49–59. https://doi.org/10.1007/s00262-008-0523-4
Dolcetti L, Peranzoni E, Ugel S et al (2010) Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF. Eur J Immunol 40(1):22–35. https://doi.org/10.1002/eji.200939903
Dumitru CA, Moses K, Trellakis S et al (2012) Neutrophils and granulocytic myeloid-derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology. Cancer Immunol Immunother 61(8):1155–1167. https://doi.org/10.1007/s00262-012-1294-5
Eruslanov E, Neuberger M, Daurkin I et al (2012) Circulating and tumor-infiltrating myeloid cell subsets in patients with bladder cancer. Int J Cancer 130(5):1109–1119. https://doi.org/10.1002/ijc.26123
Filipazzi P, Valenti R, Huber V et al (2007) Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol 25(18):2546–2553. https://doi.org/10.1200/JCO.2006.08.5829
Florcken A, Takvorian A, Singh A et al (2015) Myeloid-derived suppressor cells in human peripheral blood: optimized quantification in healthy donors and patients with metastatic renal cell carcinoma. Immunol Lett 168(2):260–267. https://doi.org/10.1016/j.imlet.2015.10.001
Fujita M, Kohanbash G, Fellows-Mayle W et al (2011) COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res 71(7):2664–2674. https://doi.org/10.1158/0008-5472.CAN-10-3055
Fultang N, Li X, Li T et al (2020) Myeloid-derived suppressor cell differentiation in cancer: transcriptional regulators and Enhanceosome-mediated mechanisms. Front Immunol 11:619253. https://doi.org/10.3389/fimmu.2020.619253
Gabrilovich D, Ishida T, Oyama T et al (1998) Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92(11):4150–4166
Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174. https://doi.org/10.1038/nri2506
Greene S, Robbins Y, Mydlarz WK et al (2020) Inhibition of MDSC trafficking with SX-682, a CXCR1/2 inhibitor, enhances NK-cell immunotherapy in head and neck cancer models. Clin Cancer Res 26(6):1420–1431. https://doi.org/10.1158/1078-0432.CCR-19-2625
Greifenberg V, Ribechini E, Rossner S et al (2009) Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development. Eur J Immunol 39(10):2865–2876. https://doi.org/10.1002/eji.200939486
Ham B, Wang N, D'Costa Z et al (2015) TNF Receptor-2 facilitates an immunosuppressive microenvironment in the liver to promote the colonization and growth of hepatic metastases. Cancer Res 75(24):5235–5247. https://doi.org/10.1158/0008-5472.CAN-14-3173
Hanson EM, Clements VK, Sinha P et al (2009) Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. J Immunol 183(2):937–944. https://doi.org/10.4049/jimmunol.0804253
Haverkamp JM, Crist SA, Elzey BD et al (2011) In vivo suppressive function of myeloid-derived suppressor cells is limited to the inflammatory site. Eur J Immunol 41(3):749–759. https://doi.org/10.1002/eji.201041069
Highfill SL, Cui Y, Giles AJ et al (2014) Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci Transl Med 6(237):237ra267. https://doi.org/10.1126/scitranslmed.3007974
Hoechst B, Ormandy LA, Ballmaier M et al (2008) A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells. Gastroenterology 135(1):234–243. https://doi.org/10.1053/j.gastro.2008.03.020
Hoechst B, Voigtlaender T, Ormandy L et al (2009) Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology 50(3):799–807. https://doi.org/10.1002/hep.23054
Holmgaard RB, Zamarin D, Li Y et al (2015) Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner. Cell Rep 13(2):412–424. https://doi.org/10.1016/j.celrep.2015.08.077
Hossain F, Al-Khami AA, Wyczechowska D et al (2015) Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol Res 3(11):1236–1247. https://doi.org/10.1158/2326-6066.CIR-15-0036
Hu X, Li B, Li X et al (2014) Transmembrane TNF-alpha promotes suppressive activities of myeloid-derived suppressor cells via TNFR2. J Immunol 192(3):1320–1331. https://doi.org/10.4049/jimmunol.1203195
Huang B, Lei Z, Zhao J et al (2007) CCL2/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers. Cancer Lett 252(1):86–92. https://doi.org/10.1016/j.canlet.2006.12.012
Huang B, Pan PY, Li Q et al (2006) Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66(2):1123–1131. https://doi.org/10.1158/0008-5472.CAN-05-1299
Ichikawa M, Williams R, Wang L et al (2011) S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res 9(2):133–148. https://doi.org/10.1158/1541-7786.MCR-10-0394
Jaufmann J, Lelis FJN, Teschner AC et al (2020) Human monocytic myeloid-derived suppressor cells impair B-cell phenotype and function in vitro. Eur J Immunol 50(1):33–47. https://doi.org/10.1002/eji.201948240
Jian SL, Chen WW, Su YC et al (2017) Glycolysis regulates the expansion of myeloid-derived suppressor cells in tumor-bearing hosts through prevention of ROS-mediated apoptosis. Cell Death Dis 8(5):e2779. https://doi.org/10.1038/cddis.2017.192
Jiang M, Chen J, Zhang W et al (2017) Interleukin-6 trans-signaling pathway promotes immunosuppressive myeloid-derived suppressor cells via suppression of suppressor of cytokine signaling 3 in breast cancer. Front Immunol 8:1840. https://doi.org/10.3389/fimmu.2017.01840
Ju JM, Nam G, Lee YK et al (2021) IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease. Proc Natl Acad Sci U S A:118 (10). https://doi.org/10.1073/pnas.2011170118
Kamran N, Kadiyala P, Saxena M et al (2017) Immunosuppressive myeloid Cells' blockade in the glioma microenvironment enhances the efficacy of immune-stimulatory gene therapy. Mol Ther 25(1):232–248. https://doi.org/10.1016/j.ymthe.2016.10.003
Khaled YS, Ammori BJ, Elkord E (2014) Increased levels of granulocytic myeloid-derived suppressor cells in peripheral blood and tumour tissue of pancreatic cancer patients. J Immunol Res 2014:879897. https://doi.org/10.1155/2014/879897
Ko JS, Zea AH, Rini BI et al (2009) Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 15(6):2148–2157. https://doi.org/10.1158/1078-0432.CCR-08-1332
Kortylewski M, Kujawski M, Wang T et al (2005) Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med 11(12):1314–1321. https://doi.org/10.1038/nm1325
Kotsakis A, Harasymczuk M, Schilling B et al (2012) Myeloid-derived suppressor cell measurements in fresh and cryopreserved blood samples. J Immunol Methods 381(1–2):14–22. https://doi.org/10.1016/j.jim.2012.04.004
Kowanetz M, Wu X, Lee J et al (2010) Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes. Proc Natl Acad Sci U S A 107(50):21248–21255. https://doi.org/10.1073/pnas.1015855107
Kujawski M, Kortylewski M, Lee H et al (2008) Stat3 mediates myeloid cell-dependent tumor angiogenesis in mice. J Clin Invest 118(10):3367–3377. https://doi.org/10.1172/JCI35213
Kumar V, Cheng P, Condamine T et al (2016a) CD45 phosphatase inhibits STAT3 transcription factor activity in myeloid cells and promotes tumor-associated macrophage differentiation. Immunity 44(2):303–315. https://doi.org/10.1016/j.immuni.2016.01.014
Kumar V, Patel S, Tcyganov E et al (2016b) The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol 37(3):208–220. https://doi.org/10.1016/j.it.2016.01.004
Kusmartsev S, Nefedova Y, Yoder D et al (2004) Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 172(2):989–999. https://doi.org/10.4049/jimmunol.172.2.989
Lang S, Bruderek K, Kaspar C et al (2018) Clinical relevance and suppressive capacity of human myeloid-derived suppressor cell subsets. Clin Cancer Res 24(19):4834–4844. https://doi.org/10.1158/1078-0432.CCR-17-3726
Le HK, Graham L, Cha E et al (2009) Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice. Int Immunopharmacol 9(7–8):900–909. https://doi.org/10.1016/j.intimp.2009.03.015
Lechner MG, Liebertz DJ, Epstein AL (2010) Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol 185(4):2273–2284. https://doi.org/10.4049/jimmunol.1000901
Lee GK, Park HJ, Macleod M et al (2002) Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division. Immunology 107(4):452–460. https://doi.org/10.1046/j.1365-2567.2002.01526.x
Lelis FJN, Jaufmann J, Singh A et al (2017) Myeloid-derived suppressor cells modulate B-cell responses. Immunol Lett 188:108–115. https://doi.org/10.1016/j.imlet.2017.07.003
Lesokhin AM, Hohl TM, Kitano S et al (2012) Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment. Cancer Res 72(4):876–886. https://doi.org/10.1158/0008-5472.CAN-11-1792
Li H, Han Y, Guo Q et al (2009) Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol 182(1):240–249. https://doi.org/10.4049/jimmunol.182.1.240
Li T, Li X, Zamani A et al (2020) C-Rel is a myeloid checkpoint for cancer immunotherapy. Nat Cancer 1(5):507–517. https://doi.org/10.1038/s43018-020-0061-3
Limagne E, Euvrard R, Thibaudin M et al (2016) Accumulation of MDSC and Th17 cells in patients with metastatic colorectal cancer predicts the efficacy of a FOLFOX-bevacizumab drug treatment regimen. Cancer Res 76(18):5241–5252. https://doi.org/10.1158/0008-5472.CAN-15-3164
Liu G, Bi Y, Shen B et al (2014) SIRT1 limits the function and fate of myeloid-derived suppressor cells in tumors by orchestrating HIF-1alpha-dependent glycolysis. Cancer Res 74(3):727–737. https://doi.org/10.1158/0008-5472.CAN-13-2584
Liu CY, Wang YM, Wang CL et al (2010) Population alterations of L-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14(−)/CD15+/CD33+ myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol 136(1):35–45. https://doi.org/10.1007/s00432-009-0634-0
Loeuillard E, Yang J, Buckarma E et al (2020) Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma. J Clin Invest 130(10):5380–5396. https://doi.org/10.1172/JCI137110
Maenhout SK, Van Lint S, Emeagi PU et al (2014) Enhanced suppressive capacity of tumor-infiltrating myeloid-derived suppressor cells compared with their peripheral counterparts. Int J Cancer 134(5):1077–1090. https://doi.org/10.1002/ijc.28449
Mao Y, Poschke I, Wennerberg E et al (2013) Melanoma-educated CD14+ cells acquire a myeloid-derived suppressor cell phenotype through COX-2-dependent mechanisms. Cancer Res 73(13):3877–3887. https://doi.org/10.1158/0008-5472.CAN-12-4115
Mastio J, Condamine T, Dominguez G et al (2019) Identification of monocyte-like precursors of granulocytes in cancer as a mechanism for accumulation of PMN-MDSCs. J Exp Med 216(9):2150–2169. https://doi.org/10.1084/jem.20181952
Medina-Echeverz J, Haile LA, Zhao F et al (2014) IFN-gamma regulates survival and function of tumor-induced CD11b+ gr-1high myeloid derived suppressor cells by modulating the anti-apoptotic molecule Bcl2a1. Eur J Immunol 44(8):2457–2467. https://doi.org/10.1002/eji.201444497
Menetrier-Caux C, Montmain G, Dieu MC et al (1998) Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. Blood 92(12):4778–4791
Meyer C, Cagnon L, Costa-Nunes CM et al (2014) Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol Immunother 63(3):247–257. https://doi.org/10.1007/s00262-013-1508-5
Mizukoshi E, Yamashita T, Arai K et al (2016) Myeloid-derived suppressor cells correlate with patient outcomes in hepatic arterial infusion chemotherapy for hepatocellular carcinoma. Cancer Immunol Immunother 65(6):715–725. https://doi.org/10.1007/s00262-016-1837-2
Mohamed E, Sierra RA, Trillo-Tinoco J et al (2020) The unfolded protein response mediator PERK governs myeloid cell-driven immunosuppression in tumors through inhibition of STING signaling. Immunity 52(4):668–682 e667. https://doi.org/10.1016/j.immuni.2020.03.004
Morales JK, Kmieciak M, Knutson KL et al (2010) GM-CSF is one of the main breast tumor-derived soluble factors involved in the differentiation of CD11b-Gr1- bone marrow progenitor cells into myeloid-derived suppressor cells. Breast Cancer Res Treat 123(1):39–49. https://doi.org/10.1007/s10549-009-0622-8
Movahedi K, Guilliams M, Van den Bossche J et al (2008) Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 111(8):4233–4244. https://doi.org/10.1182/blood-2007-07-099226
Mundy-Bosse BL, Young GS, Bauer T et al (2011) Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4(+) T cells from patients with GI malignancy. Cancer Immunol Immunother 60(9):1269–1279. https://doi.org/10.1007/s00262-011-1029-z
Najjar YG, Rayman P, Jia X et al (2017) Myeloid-derived suppressor cell subset accumulation in renal cell carcinoma parenchyma is associated with Intratumoral expression of IL1beta, IL8, CXCL5, and Mip-1alpha. Clin Cancer Res 23(9):2346–2355. https://doi.org/10.1158/1078-0432.CCR-15-1823
Nefedova Y, Nagaraj S, Rosenbauer A et al (2005) Regulation of dendritic cell differentiation and antitumor immune response in cancer by pharmacologic-selective inhibition of the janus-activated kinase 2/signal transducers and activators of transcription 3 pathway. Cancer Res 65(20):9525–9535. https://doi.org/10.1158/0008-5472.CAN-05-0529
Niedermeier M, Reich B, Rodriguez Gomez M et al (2009) CD4+ T cells control the differentiation of Gr1+ monocytes into fibrocytes. Proc Natl Acad Sci U S A 106(42):17892–17897. https://doi.org/10.1073/pnas.0906070106
Noman MZ, Desantis G, Janji B et al (2014) PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med 211(5):781–790. https://doi.org/10.1084/jem.20131916
Obermajer N, Muthuswamy R, Lesnock J et al (2011a) Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood 118(20):5498–5505. https://doi.org/10.1182/blood-2011-07-365825
Obermajer N, Muthuswamy R, Odunsi K et al (2011b) PGE(2)-induced CXCL12 production and CXCR4 expression controls the accumulation of human MDSCs in ovarian cancer environment. Cancer Res 71(24):7463–7470. https://doi.org/10.1158/0008-5472.CAN-11-2449
Ornstein MC, Diaz-Montero CM, Rayman P et al (2018) Myeloid-derived suppressors cells (MDSC) correlate with clinicopathologic factors and pathologic complete response (pCR) in patients with urothelial carcinoma (UC) undergoing cystectomy. Urol Oncol 36(9):405–412. https://doi.org/10.1016/j.urolonc.2018.02.018
Otvos B, Silver DJ, Mulkearns-Hubert EE et al (2016) Cancer stem cell-secreted macrophage migration inhibitory factor stimulates myeloid derived suppressor cell function and facilitates glioblastoma immune evasion. Stem Cells 34(8):2026–2039. https://doi.org/10.1002/stem.2393
Ouzounova M, Lee E, Piranlioglu R et al (2017) Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. Nat Commun 8:14979. https://doi.org/10.1038/ncomms14979
Pan PY, Ma G, Weber KJ et al (2010) Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer. Cancer Res 70(1):99–108. https://doi.org/10.1158/0008-5472.CAN-09-1882
Panni RZ, Sanford DE, Belt BA et al (2014) Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer. Cancer Immunol Immunother 63(5):513–528. https://doi.org/10.1007/s00262-014-1527-x
Peereboom DM, Alban TJ, Grabowski MM et al (2019) Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells. JCI. Insight 4(22). https://doi.org/10.1172/jci.insight.130748
Peng D, Tanikawa T, Li W et al (2016) Myeloid-derived suppressor cells endow stem-like qualities to breast cancer cells through IL6/STAT3 and NO/NOTCH cross-talk signaling. Cancer Res 76(11):3156–3165. https://doi.org/10.1158/0008-5472.CAN-15-2528
Polz J, Remke A, Weber S et al (2014) Myeloid suppressor cells require membrane TNFR2 expression for suppressive activity. Immun Inflamm Dis 2(2):121–130. https://doi.org/10.1002/iid3.19
Porembka MR, Mitchem JB, Belt BA et al (2012) Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth. Cancer Immunol Immunother 61(9):1373–1385. https://doi.org/10.1007/s00262-011-1178-0
Raber P, Ochoa AC, Rodriguez PC (2012) Metabolism of L-arginine by myeloid-derived suppressor cells in cancer: mechanisms of T cell suppression and therapeutic perspectives. Immunol Investig 41(6–7):614–634. https://doi.org/10.3109/08820139.2012.680634
Raber PL, Thevenot P, Sierra R et al (2014) Subpopulations of myeloid-derived suppressor cells impair T cell responses through independent nitric oxide-related pathways. Int J Cancer 134(12):2853–2864. https://doi.org/10.1002/ijc.28622
Raychaudhuri B, Rayman P, Huang P et al (2015) Myeloid derived suppressor cell infiltration of murine and human gliomas is associated with reduction of tumor infiltrating lymphocytes. J Neuro-Oncol 122(2):293–301. https://doi.org/10.1007/s11060-015-1720-6
Raychaudhuri B, Rayman P, Ireland J et al (2011) Myeloid-derived suppressor cell accumulation and function in patients with newly diagnosed glioblastoma. Neuro-Oncology 13(6):591–599. https://doi.org/10.1093/neuonc/nor042
Rodrigues JC, Gonzalez GC, Zhang L et al (2010) Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor cell-like properties. Neuro-Oncology 12(4):351–365. https://doi.org/10.1093/neuonc/nop023
Rodriguez PC, Ernstoff MS, Hernandez C et al (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69(4):1553–1560. https://doi.org/10.1158/0008-5472.CAN-08-1921
Rodriguez PC, Hernandez CP, Quiceno D et al (2005) Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J Exp Med 202(7):931–939. https://doi.org/10.1084/jem.20050715
Rodriguez PC, Quiceno DG, Zabaleta J et al (2004) Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 64(16):5839–5849. https://doi.org/10.1158/0008-5472.CAN-04-0465
Romano A, Parrinello NL, Vetro C et al (2015) Circulating myeloid-derived suppressor cells correlate with clinical outcome in Hodgkin lymphoma patients treated up-front with a risk-adapted strategy. Br J Haematol 168(5):689–700. https://doi.org/10.1111/bjh.13198
Sceneay J, Chow MT, Chen A et al (2012) Primary tumor hypoxia recruits CD11b+/Ly6Cmed/Ly6G+ immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche. Cancer Res 72(16):3906–3911. https://doi.org/10.1158/0008-5472.CAN-11-3873
Schouppe E, Mommer C, Movahedi K et al (2013) Tumor-induced myeloid-derived suppressor cell subsets exert either inhibitory or stimulatory effects on distinct CD8+ T-cell activation events. Eur J Immunol 43(11):2930–2942. https://doi.org/10.1002/eji.201343349
Seubert B, Grunwald B, Kobuch J et al (2015) Tissue inhibitor of metalloproteinases (TIMP)-1 creates a premetastatic niche in the liver through SDF-1/CXCR4-dependent neutrophil recruitment in mice. Hepatology 61(1):238–248. https://doi.org/10.1002/hep.27378
Shen P, Wang A, He M et al (2014) Increased circulating Lin(−/low) CD33(+) HLA-DR(−) myeloid-derived suppressor cells in hepatocellular carcinoma patients. Hepatol Res 44(6):639–650. https://doi.org/10.1111/hepr.12167
Sheng IY, Diaz-Montero CM, Rayman P et al (2020) Blood myeloid-derived suppressor cells correlate with neutrophil-to-lymphocyte ratio and overall survival in metastatic urothelial carcinoma. Target Oncol 15(2):211–220. https://doi.org/10.1007/s11523-020-00707-z
Shime H, Maruyama A, Yoshida S et al (2017) Toll-like receptor 2 ligand and interferon-gamma suppress anti-tumor T cell responses by enhancing the immunosuppressive activity of monocytic myeloid-derived suppressor cells. Onco Targets Ther 7(1):e1373231. https://doi.org/10.1080/2162402X.2017.1373231
Shirota Y, Shirota H, Klinman DM (2012) Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells. J Immunol 188(4):1592–1599. https://doi.org/10.4049/jimmunol.1101304
Sinha P, Clements VK, Bunt SK et al (2007b) Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 179(2):977–983. https://doi.org/10.4049/jimmunol.179.2.977
Sinha P, Clements VK, Fulton AM et al (2007a) Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 67(9):4507–4513. https://doi.org/10.1158/0008-5472.CAN-06-4174
Solito S, Falisi E, Diaz-Montero CM et al (2011) A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells. Blood 118(8):2254–2265. https://doi.org/10.1182/blood-2010-12-325753
Song X, Krelin Y, Dvorkin T et al (2005) CD11b+/gr-1+ immature myeloid cells mediate suppression of T cells in mice bearing tumors of IL-1beta-secreting cells. J Immunol 175(12):8200–8208. https://doi.org/10.4049/jimmunol.175.12.8200
Spiegel A, Brooks MW, Houshyar S et al (2016) Neutrophils suppress intraluminal NK cell-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells. Cancer Discov 6(6):630–649. https://doi.org/10.1158/2159-8290.CD-15-1157
Srivastava MK, Sinha P, Clements VK et al (2010) Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res 70(1):68–77. https://doi.org/10.1158/0008-5472.CAN-09-2587
Szczerba BM, Castro-Giner F, Vetter M et al (2019) Neutrophils escort circulating tumour cells to enable cell cycle progression. Nature 566(7745):553–557. https://doi.org/10.1038/s41586-019-0915-y
Taheri F, Ochoa JB, Faghiri Z et al (2001) L-arginine regulates the expression of the T-cell receptor zeta chain (CD3zeta) in Jurkat cells. Clin Cancer Res 7(3 Suppl):958s–965s
Tannenbaum CS, Rayman PA, Pavicic PG et al (2019) Mediators of inflammation-driven expansion, trafficking, and function of tumor-infiltrating MDSCs. Cancer Immunol Res 7(10):1687–1699. https://doi.org/10.1158/2326-6066.CIR-18-0578
Tavazoie MF, Pollack I, Tanqueco R et al (2018) LXR/ApoE activation restricts innate immune suppression in cancer. Cell 172 (4):825-840:e818. https://doi.org/10.1016/j.cell.2017.12.026
Thevenot PT, Sierra RA, Raber PL et al (2014) The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors. Immunity 41(3):389–401. https://doi.org/10.1016/j.immuni.2014.08.015
Ugolini A, Tyurin VA, Tyurina YY et al (2020) Polymorphonuclear myeloid-derived suppressor cells limit antigen cross-presentation by dendritic cells in cancer. JCI. Insight 5(15). https://doi.org/10.1172/jci.insight.138581
Van Overmeire E, Stijlemans B, Heymann F et al (2016) M-CSF and GM-CSF receptor signaling differentially regulate monocyte maturation and macrophage polarization in the tumor microenvironment. Cancer Res 76(1):35–42. https://doi.org/10.1158/0008-5472.CAN-15-0869
Veglia F, Hashimoto A, Dweep H et al (2021) Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice. J Exp Med 218(4). https://doi.org/10.1084/jem.20201803
Veglia F, Tyurin VA, Blasi M et al (2019) Fatty acid transport protein 2 reprograms neutrophils in cancer. Nature 569(7754):73–78. https://doi.org/10.1038/s41586-019-1118-2
Veltman JD, Lambers ME, van Nimwegen M et al (2010) COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer 10:464. https://doi.org/10.1186/1471-2407-10-464
Vetsika EK, Koinis F, Gioulbasani M et al (2014) A circulating subpopulation of monocytic myeloid-derived suppressor cells as an independent prognostic/predictive factor in untreated non-small lung cancer patients. J Immunol Res 2014:659294. https://doi.org/10.1155/2014/659294
Vincent J, Mignot G, Chalmin F et al (2010) 5-fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res 70(8):3052–3061. https://doi.org/10.1158/0008-5472.CAN-09-3690
Vuk-Pavlovic S, Bulur PA, Lin Y et al (2010) Immunosuppressive CD14+HLA-DRlow/− monocytes in prostate cancer. Prostate 70(4):443–455. https://doi.org/10.1002/pros.21078
Waight JD, Hu Q, Miller A et al (2011) Tumor-derived G-CSF facilitates neoplastic growth through a granulocytic myeloid-derived suppressor cell-dependent mechanism. PLoS One 6(11):e27690. https://doi.org/10.1371/journal.pone.0027690
Waight JD, Netherby C, Hensen ML et al (2013) Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis. J Clin Invest 123(10):4464–4478. https://doi.org/10.1172/JCI68189
Wang G, Lu X, Dey P et al (2016) Targeting YAP-dependent MDSC infiltration impairs tumor progression. Cancer Discov 6(1):80–95. https://doi.org/10.1158/2159-8290.CD-15-0224
Wang Y, Schafer CC, Hough KP et al (2018) Myeloid-derived suppressor cells impair B cell responses in lung cancer through IL-7 and STAT5. J Immunol 201(1):278–295. https://doi.org/10.4049/jimmunol.1701069
Wang J, Shirota Y, Bayik D et al (2015) Effect of TLR agonists on the differentiation and function of human monocytic myeloid-derived suppressor cells. J Immunol 194(9):4215–4221. https://doi.org/10.4049/jimmunol.1402004
Wang D, Sun H, Wei J et al (2017a) CXCL1 is critical for Premetastatic niche formation and metastasis in colorectal cancer. Cancer Res 77(13):3655–3665. https://doi.org/10.1158/0008-5472.CAN-16-3199
Wang Z, Till B, Gao Q (2017b) Chemotherapeutic agent-mediated elimination of myeloid-derived suppressor cells. Onco Targets Ther 6(7):e1331807. https://doi.org/10.1080/2162402X.2017.1331807
Wang J, Yang J (2016) Identification of CD4(+)CD25(+)CD127(−) regulatory T cells and CD14(+)HLA(−)DR(−)/low myeloid-derived suppressor cells and their roles in the prognosis of breast cancer. Biomed Rep 5(2):208–212. https://doi.org/10.3892/br.2016.694
Wang Y, Yin K, Tian J et al (2019) Granulocytic myeloid-derived suppressor cells promote the Stemness of colorectal cancer cells through Exosomal S100A9. Adv Sci (Weinh) 6(18):1901278. https://doi.org/10.1002/advs.201901278
Weide B, Martens A, Zelba H et al (2014) Myeloid-derived suppressor cells predict survival of patients with advanced melanoma: comparison with regulatory T cells and NY-ESO-1- or melan-A-specific T cells. Clin Cancer Res 20(6):1601–1609. https://doi.org/10.1158/1078-0432.CCR-13-2508
Wu P, Wu D, Ni C et al (2014) gammadeltaT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer. Immunity 40(5):785–800. https://doi.org/10.1016/j.immuni.2014.03.013
Xu XD, Hu J, Wang M et al (2016) Circulating myeloid-derived suppressor cells in patients with pancreatic cancer. Hepatobiliary Pancreat Dis Int 15(1):99–105. https://doi.org/10.1016/s1499-3872(15)60413-1
Xu X, Meng Q, Erben U et al (2017) Myeloid-derived suppressor cells promote B-cell production of IgA in a TNFR2-dependent manner. Cell Mol Immunol 14(7):597–606. https://doi.org/10.1038/cmi.2015.103
Yamauchi Y, Safi S, Blattner C et al (2018) Circulating and tumor myeloid-derived suppressor cells in Resectable non-small cell lung cancer. Am J Respir Crit Care Med 198(6):777–787. https://doi.org/10.1164/rccm.201708-1707OC
Yan HH, Pickup M, Pang Y et al (2010) Gr-1+CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung. Cancer Res 70(15):6139–6149. https://doi.org/10.1158/0008-5472.CAN-10-0706
Yang L, DeBusk LM, Fukuda K et al (2004) Expansion of myeloid immune suppressor gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6(4):409–421. https://doi.org/10.1016/j.ccr.2004.08.031
Youn JI, Collazo M, Shalova IN et al (2012) Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J Leukoc Biol 91(1):167–181. https://doi.org/10.1189/jlb.0311177
Youn JI, Kumar V, Collazo M et al (2013) Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer. Nat Immunol 14(3):211–220. https://doi.org/10.1038/ni.2526
Youn JI, Nagaraj S, Collazo M et al (2008) Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol 181(8):5791–5802. https://doi.org/10.4049/jimmunol.181.8.5791
Young MR, Wright MA, Pandit R (1997) Myeloid differentiation treatment to diminish the presence of immune-suppressive CD34+ cells within human head and neck squamous cell carcinomas. J Immunol 159(2):990–996
Yu J, Du W, Yan F et al (2013) Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer. J Immunol 190(7):3783–3797. https://doi.org/10.4049/jimmunol.1201449
Yu SJ, Ma C, Heinrich B et al (2019) Targeting the crosstalk between cytokine-induced killer cells and myeloid-derived suppressor cells in hepatocellular carcinoma. J Hepatol 70(3):449–457. https://doi.org/10.1016/j.jhep.2018.10.040
Zhang Q, Ma C, Duan Y et al (2021) Gut microbiome directs hepatocytes to recruit MDSCs and promote cholangiocarcinoma. Cancer Discov 11(5):1248–1267. https://doi.org/10.1158/2159-8290.CD-20-0304
Zhao X, Rong L, Zhao X et al (2012) TNF signaling drives myeloid-derived suppressor cell accumulation. J Clin Invest 122(11):4094–4104. https://doi.org/10.1172/JCI64115
Zhong H, Gutkin DW, Han B et al (2014) Origin and pharmacological modulation of tumor-associated regulatory dendritic cells. Int J Cancer 134(11):2633–2645. https://doi.org/10.1002/ijc.28590
Zhong LM, Liu ZG, Zhou X et al (2019) Expansion of PMN-myeloid derived suppressor cells and their clinical relevance in patients with oral squamous cell carcinoma. Oral Oncol 95:157–163. https://doi.org/10.1016/j.oraloncology.2019.06.004
Zhu Y, Knolhoff BL, Meyer MA et al (2014) CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res 74(18):5057–5069. https://doi.org/10.1158/0008-5472.CAN-13-3723
Zoso A, Mazza EM, Bicciato S et al (2014) Human fibrocytic myeloid-derived suppressor cells express IDO and promote tolerance via Treg-cell expansion. Eur J Immunol 44(11):3307–3319. https://doi.org/10.1002/eji.201444522
Acknowledgments
The authors would like to thank Dr. Erin Mulkearns-Hubert for editorial assistance and Ms. Amanda Mendelsohn for illustrations. Work in the Lathia laboratory is supported by the Cleveland Clinic, Case Comprehensive Cancer Center, the American Brain Tumor Association, National Brain Tumor Society, and NIH R01 NS109742, R01 NS117104, P01 CA245705 (J.L.) and K99 CA248611 (D.B.).
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Bayik, D., Lee, J., Lathia, J.D. (2022). The Role of Myeloid-Derived Suppressor Cells in Tumor Growth and Metastasis. In: Klink, M., Szulc-Kielbik, I. (eds) Interaction of Immune and Cancer Cells. Experientia Supplementum, vol 113. Springer, Cham. https://doi.org/10.1007/978-3-030-91311-3_7
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