Targeting Myeloid-Derived Suppressor Cells in Ovarian Cancer

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that exhibit immunosuppressive activity. They also directly stimulate tumor cell proliferation, metastasis, and angiogenesis. In ovarian cancer, there are increased numbers of circulating or tumor-infiltrating MDSCs, and increased frequencies of MDSCs are associated with a poor prognosis or an advanced clinical stage. Moreover, in murine models of ovarian cancer, MDSC depletion has shown significant growth-inhibitory effects and enhanced the therapeutic efficacy of existing anticancer therapies. In this review, we summarize the current knowledge on MDSC biology, clinical significance of MDSC, and potential MDSC-targeting strategies in ovarian cancer.

Keywords: MDSC; ovarian cancer; survival; therapeutic target; tumor microenvironment.

Figure 1

Functions of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME). 1) Immunosuppressive functions of MDSC; in TME, MDSC block T cell differentiation and inhibit the proliferation of T cell/NK cell by removing L-arginine. MDSC also inhibit the activities and diminish interferon response of T cell/NK cell via the production of ROS/NO. Increased PD-L1 expression in MDSC can lead to the downregulation of T cell function via the engagement of PD-1 in T cells. 2) Nonimmune activities of MDSC; MDSC promote cancer progression by inducing angiogenesis and tumor invasion via the production of VEGF, bFGF, Bv8, and MMP-9. Moreover, MDSC stimulate the metastatic activities of cancer cell by facilitating EMT and creating “premetastatic niches.” MDSC also induce “stemness” in certain cancers, which might be associated with resistance to chemotherapy or radiotherapy.