Myeloid-Derived Suppressor Cells as Key Players and Promising Therapy Targets in Prostate Cancer

Abstract

Prostate cancer (PC) is the second most often diagnosed malignancy in men and one of the major causes of cancer death worldwide. Despite genetic predispositions, environmental factors, including a high-fat diet, obesity, a sedentary lifestyle, infections of the prostate, and exposure to chemicals or ionizing radiation, play a crucial role in PC development. Moreover, due to a lack of, or insufficient T-cell infiltration and its immunosuppressive microenvironment, PC is frequently classified as a “cold” tumor. This is related to the absence of tumor-associated antigens, the lack of T-cell activation and their homing into the tumor bed, and the presence of immunological cells with regulatory functions, including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg), and tumor-associated macrophages (TAMs). All of them, by a variety of means, hamper anti-tumor immune response in the tumor microenvironment (TME), stimulating tumor growth and the formation of metastases. Therefore, they emerge as potential anti-cancer therapy targets. This article is focused on the function and role of MDSCs in the initiation and progression of PC. Clinical trials directly targeting this cell population or affecting its biological functions, thus limiting its pro-tumorigenic activity, are also presented.

Profound immunomodulatory effects of 225Ac-NM600 drive enhanced anti-tumor response in prostate cancer

“…Even though a higher level of cytotoxic T cells usually indicates greater anti-tumor effects (44)(45)(46), that is not necessarily true for prostate cancer (47). Some studies have reported that an increase in cytotoxic T lymphocytes (CTL) in prostate cancer TME correlated with a worse prognosis (48)(49)(50), mainly because CTLs were neutralized by anti-inflammatory and immunosuppressive mediators such as MDSCs and Tregs (50,51). Thus, generally, a metric more reflective of the immunological status of the TME is the ratio of infiltrating CTLs to suppressive cells (52).…”

Functional plasticity of neutrophils after low- or high-dose irradiation in cancer treatment – A mini review

“…Radiation induces the infiltration of MDSCs into different types of tumors, with either low- or high- dose radiation ( 54 , 60 ). The development of bone marrow-derived myeloid cells, including TAM and MDSCs, is dependent on CSF1/CSF1 receptor (CSF1R) ( 33 , 61 , 62 ).…”

The Role of Myeloid-Derived Suppressor Cells in the Treatment of Pancreatic Cancer

“…Human MDSCs do not express GR-1 thus their classification characteristics are more complex, usually, the phenotype of MDSCs in human peripheral blood mononuclear cells (PBMCs) is CD33 + , CD11b + , and HLA-DR low/− , and human MDSCs are classified as G-MDSCs and M-MDSCs based on the presence of CD15 and CD14 marker. 29 Another human MDSCs subpopulation is early MDSCs (e-MDSCs) that still do not acquire a granulocytic or monocytic phenotype, which is characterized phenotypically by (CD3, CD20, CD56) − , CD33 + , CD11b + , and HLA-DR − . 30 , 31 Additional markers of human MDSCs found by flow cytometry, such as CD16, CD38, and LOX-1, may provide a reference for subsequent typing.…”