The Role of Myeloid-derived Suppressor Cells in Gastrointestinal Cancer

Overview

Journal Cancer Commun (Lond)

Publisher Wiley

Specialty Oncology

Date 2021 Mar 27

PMID 33773092

Citations 15

Authors

Cheng Cui

Penglin Lan

Li Fu

Affiliations

Soon will be listed here.

Abstract

Gastrointestinal (GI) cancer encompasses a range of malignancies that originate in the digestive system, which together represent the most common form of cancer diagnosed worldwide. However, despite numerous advances in both diagnostics and treatment, the incidence and mortality rate of GI cancer are on the rise. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that increase in number under certain pathological conditions, such as infection and inflammation, and this expansion is of particular relevance to cancer. MDSCs are heavily involved in the regulation of the immune system and act to dampen its response to tumors, favoring the escape of tumor cells from immunosurveillance and increasing both metastasis and recurrence. Several recent studies have supported the use of MDSCs as a prognostic and predictive biomarker in patients with cancer, and potentially as a novel treatment target. In the present review, the mechanisms underlying the immunosuppressive functions of MDSCs are described, and recent researches concerning the involvement of MDSCs in the progression, prognosis, and therapies of GI cancer are reviewed. The aim of this work was to present the development of novel treatments targeting MDSCs in GI cancer in the hope of improving outcomes for patients with this condition.

Citing Articles

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References

Zhang B, Wang Z, Wu L, Zhang M, Li W, Ding J . Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma. PLoS One. 2013; 8(2):e57114. PMC: 3577767. DOI: 10.1371/journal.pone.0057114. View

Holmgaard R, Zamarin D, Li Y, Gasmi B, Munn D, Allison J . Tumor-Expressed IDO Recruits and Activates MDSCs in a Treg-Dependent Manner. Cell Rep. 2015; 13(2):412-24. PMC: 5013825. DOI: 10.1016/j.celrep.2015.08.077. View

Albrengues J, Shields M, Ng D, Park C, Ambrico A, Poindexter M . Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science. 2018; 361(6409). PMC: 6777850. DOI: 10.1126/science.aao4227. View

Chen M, Kuan F, Yen T, Lu M, Lin P, Chung Y . 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. 2014; 5(18):8716-28. PMC: 4226716. DOI: 10.18632/oncotarget.2368. View

Huang T, Fu L . The immune landscape of esophageal cancer. Cancer Commun (Lond). 2019; 39(1):79. PMC: 6878621. DOI: 10.1186/s40880-019-0427-z. View

Teng F, Meng X, Kong L, Mu D, Zhu H, Liu S . Tumor-infiltrating lymphocytes, forkhead box P3, programmed death ligand-1, and cytotoxic T lymphocyte-associated antigen-4 expressions before and after neoadjuvant chemoradiation in rectal cancer. Transl Res. 2015; 166(6):721-732.e1. DOI: 10.1016/j.trsl.2015.06.019. View

Tanikawa T, Wilke C, Kryczek I, Chen G, Kao J, Nunez G . Interleukin-10 ablation promotes tumor development, growth, and metastasis. Cancer Res. 2011; 72(2):420-9. PMC: 3261323. DOI: 10.1158/0008-5472.CAN-10-4627. View

Jayakumar A, Bothwell A . Functional Diversity of Myeloid-Derived Suppressor Cells: The Multitasking Hydra of Cancer. J Immunol. 2019; 203(5):1095-1103. PMC: 6703177. DOI: 10.4049/jimmunol.1900500. View

Huang H, Zhang G, Li G, Ma H, Zhang X . Circulating CD14(+)HLA-DR(-/low) myeloid-derived suppressor cell is an indicator of poor prognosis in patients with ESCC. Tumour Biol. 2015; 36(10):7987-96. DOI: 10.1007/s13277-015-3426-y. View

10.

Wu T, Wu X, Wang H, Chen L . Immune contexture defined by single cell technology for prognosis prediction and immunotherapy guidance in cancer. Cancer Commun (Lond). 2019; 39(1):21. PMC: 6471962. DOI: 10.1186/s40880-019-0365-9. View

11.

Huang B, Pan P, Li Q, Sato A, Levy D, Bromberg J . 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. 2006; 66(2):1123-31. DOI: 10.1158/0008-5472.CAN-05-1299. View

12.

Delano M, Scumpia P, Weinstein J, Coco D, Nagaraj S, Kelly-Scumpia K . MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med. 2007; 204(6):1463-74. PMC: 2118626. DOI: 10.1084/jem.20062602. View

13.

Kobayashi M, Chung J, Beg M, Arriaga Y, Verma U, Courtney K . Blocking Monocytic Myeloid-Derived Suppressor Cell Function via Anti-DC-HIL/GPNMB Antibody Restores the Integrity of T Cells from Cancer Patients. Clin Cancer Res. 2018; 25(2):828-838. PMC: 7315386. DOI: 10.1158/1078-0432.CCR-18-0330. View

14.

De Cicco P, Ercolano G, Ianaro A . The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion. Front Immunol. 2020; 11:1680. PMC: 7406792. DOI: 10.3389/fimmu.2020.01680. View

15.

Sun H, Zhou X, Xue Y, Wang K, Shen Y, Mao J . Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma. World J Gastroenterol. 2012; 18(25):3303-9. PMC: 3391769. DOI: 10.3748/wjg.v18.i25.3303. View

16.

Kitamura T, Fujishita T, Loetscher P, Revesz L, Hashida H, Kizaka-Kondoh S . Inactivation of chemokine (C-C motif) receptor 1 (CCR1) suppresses colon cancer liver metastasis by blocking accumulation of immature myeloid cells in a mouse model. Proc Natl Acad Sci U S A. 2010; 107(29):13063-8. PMC: 2919974. DOI: 10.1073/pnas.1002372107. View

17.

Serafini P, Meckel K, Kelso M, Noonan K, Califano J, Koch W . Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med. 2006; 203(12):2691-702. PMC: 2118163. DOI: 10.1084/jem.20061104. View

18.

Gao K, Wu J . National trend of gastric cancer mortality in China (2003-2015): a population-based study. Cancer Commun (Lond). 2019; 39(1):24. PMC: 6498569. DOI: 10.1186/s40880-019-0372-x. View

19.

Jayaraman P, Parikh F, Newton J, Hanoteau A, Rivas C, Krupar R . TGF-β1 programmed myeloid-derived suppressor cells (MDSC) acquire immune-stimulating and tumor killing activity capable of rejecting established tumors in combination with radiotherapy. Oncoimmunology. 2018; 7(10):e1490853. PMC: 6169570. DOI: 10.1080/2162402X.2018.1490853. View

20.

Chiu D, Tse A, Xu I, Cui J, Lai R, Li L . Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma. Nat Commun. 2017; 8(1):517. PMC: 5593860. DOI: 10.1038/s41467-017-00530-7. View