Abstract
Several lines of research are being investigated to better understand mechanisms implicated in response or resistance to immune checkpoint blockade in prostate cancer (PCa). Myeloid-derived suppressor cells (MDSCs) have emerged as a major mediator of immunosuppression in the tumor microenvironment that promotes progression of various tumor types. The main mechanisms underlying MDSC-induced immunosuppression are currently being explored and strategies to enhance anti-tumor immune response via MDSC targeting are being tested. However, the role of MDSCs in PCa remains elusive. In this review, we aim to summarize and present the state-of-the-art knowledge on current methodologies to phenotypically and metabolically characterize MDSCs in PCa. We describe how these characteristics may be linked with MDSC function and may influence the clinical outcomes of patients with PCa. Finally, we briefly discuss emerging strategies being employed to therapeutically target MDSCs and potentiate the long-overdue improvement in the efficacy of immunotherapy in patients with PCa.
Highlights
The role of immunotherapy in the management of patients with prostate cancer (PCa) is controversial
Each has discrete immunosuppressive properties including inhibition of T-cell activation [22], dendritic cell maturation [23], induction of anergy of natural killer cells [24], and promotion of a de novo expansion of Tregs [25] in different types of malignancies. In addition to their immune-suppressive properties, Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME) can differentiate into endothelial cells, fibroblasts, tumor-associated macrophages (TAMs) [26], and osteoclasts [27] under the influence of chemokines released by tumor cells (Figure 1) and play a pivotal role in the establishment of the premetastatic niche
Wen et al focused on a G-MDSC subpopulation, defined as CD11b+CD33+CD15+ cells, and showed that these cells were upregulated in the stroma of metastatic sites compared to the stroma of primary tumors [38]
Summary
The role of immunotherapy in the management of patients with prostate cancer (PCa) is controversial. The main premise being considered is that PCa develops potent immunosuppressive mechanisms, limiting the ability of the host immune system to detect cancer cells and control tumor growth. These include the negative regulators of T-cell function, such as CTLA-4 and PD-1 [13], and the immune camouflage (low levels of surface MHC and low mutational load) of PCa cells [14]. Complex interactions between innate and adaptive immune compartments, as well as the role of the endothelial cells and the vasculature, have been considered to function towards the establishment of cell-mediated immunosuppression [15]
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