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Myeloid-Derived Suppressor Cells (MDSCs) in Ovarian Cancer-Looking Back and Forward.

ABSTRACT: Myeloid-derived suppressor cells (MDSCs) play a significant role in the immune system and have been extensively studied in cancer. MDSCs are a heterogeneous population of myeloid cells that accumulate in the tumor microenvironment. Consequently, the high abundance of these cells often leads to immunosuppression, tumor growth, treatment failure, and poor prognosis. Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female genital tract. Currently, there is a lack of effective clinical strategies for the treatment of ovarian cancer. Although several studies underline the negative role of human MDSCs in ovarian cancer, this topic is still understudied. The works on MDSCs are summarized here, along with an explanation of why focusing on these cells would be a promising approach for treating ovarian cancer patients.

SUBMITTER: Okla K

PROVIDER: S-EPMC10377883 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Myeloid-Derived Suppressor Cells (MDSCs) in Ovarian Cancer-Looking Back and Forward.

Okła Karolina K

Cells 20230722 14

Myeloid-derived suppressor cells (MDSCs) play a significant role in the immune system and have been extensively studied in cancer. MDSCs are a heterogeneous population of myeloid cells that accumulate in the tumor microenvironment. Consequently, the high abundance of these cells often leads to immunosuppression, tumor growth, treatment failure, and poor prognosis. Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female genital tract ...[more]

PMID: 37508575

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Project description:The presence of tumor infiltrating lymphocytes (TILs) is associated with a longer overall survival in advanced stage epithelial ovarian cancer. Despite the prognostic impact of TILs, response to checkpoint-inhibitors and antigen-specific active immunotherapy is limited in ovarian cancer. The goal of our study was to investigate the interaction between ovarian cancer and the innate and adaptive immune system in the ID8-fLuc syngeneic ovarian cancer mouse model. For the in vivo experiments C57BL/6, B6.129S7-Rag1tm1Mom/J, and B6.129P2(SJL)-Myd88tm1.1Defr/J mice were inoculated with ID8-fLuc. In vivo depletion experiments were performed using clodronate liposomes (CL), anti-CD8a, anti-GR1, anti-colony stimulating factor 1 (anti-CSF1), and TMβ1 (anti-CD122). Immune read out was performed by fluorescent activated cell sorting analysis for effector T cells, regulatory T cells, natural killer cells, B cells, macrophages, and myeloid derived suppressor cells (MDSC), immunohistochemistry for MDSC and tumor-associated macrophages (TAM) and immunofluorescence for M1 and M2 TAM in the vascular context. The effect of MDSC on T cell proliferation and phenotype were studied in vitro. We discovered that the absence of T and B cells did not influence tumor growth or survival of B6.129S7-Rag1tm1Mom/J mice compared to immunocompetent C57BL/6 mice. CL-induced macrophage depletion promoted tumor proliferation and shortened survival in C57BL/6 mice (p = 0.004) and in B6.129S7-Rag1tm1Mom/J mice (p = 0.0005). During CL treatment, we observed a clear increase of pro-inflammatory cytokines (p ≤ 0.02) and monocytic MDSC (p ≤ 0.01). Selective depletion of MDSC by anti-GR1 improved survival, certainly in comparison to mice treated with anti-CSF1 (p = 0.01-median survival 91 vs. 67.5 days). B6.129P2(SJL)-Myd88tm1.1Defr/J mice displayed to a longer median survival compared to C57BL/6 mice (90 vs. 76 days). MDSC activated by ID8-fLuc conditioned medium or ascites of tumor-bearing mice showed T cell suppressive functions in vitro. Based on these findings, we conclude that the adaptive immune system does not efficiently control tumor growth in the ID8-fLuc model. In addition, we discovered a prominent role for MDSC as the driver of immunosuppression in the ID8-fLuc ovarian cancer mouse model.

Dataset Information

Myeloid-Derived Suppressor Cells (MDSCs) in Ovarian Cancer-Looking Back and Forward.

Publications

Myeloid-Derived Suppressor Cells (MDSCs) in Ovarian Cancer-Looking Back and Forward.

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