Myeloid-Derived Suppressor Cells

Abstract

Myeloid cells evolutionary developed as a major mechanism to protect the host. They evolved as a critical barrier against infections and are important contributors to tissue remodeling. However, in cancer, myeloid cells are largely converted to serve a new master – tumor cells. This process is epitomized by myeloid-derived suppressor cells (MDSC). These cells are closely related to neutrophils and monocytes. MDSC are not present at steady state in healthy individuals and appear in cancer and pathological conditions associated with chronic inflammation or stress. These cells have emerged as an important contributor to tumor progression. In recent years, ample evidence supports a key role of MDSC in immune suppression in cancer, as well as their prominent role in tumor angiogenesis, drug resistance, and promotion of tumor metastases. MDSC have a fascinating biology and are implicated in limiting the effects of cancer immunotherapy. Therefore, targeting these cells may represent an attractive therapeutic opportunity.

Neutralization of IL-8 decreases tumor PMN-MDSCs and reduces mesenchymalization of claudin-low triple-negative breast cancer

“…Among them, tumor recruitment and localization of MDSCs represent one major impediment to effective antitumor immune responses. MDSCs can be subdivided into two groups: M-MDSCs, which are phenotypically and morphologically comparable to monocytes, and PMN-MDSCs, which are comparable to neutrophils (58,59). Once they accumulate at the tumor site, MDSCs exert a suppressive role on immune cells, mainly on T cells, via several immune-suppressive factors, including arginase-1, iNOS, TGF-β, IL-10, and ROS, among others.…”

Myeloid-Derived Suppressor Cells in Infection: A General Overview

“…MDSC exercise their immunosuppressive activities through various mechanisms, including the generation of high levels of inducible nitric oxide (iNOS, mainly M-MDSC) and reactive oxygen species (ROS, mainly PMN-MDSC) that induce the nitration of the T-cell receptor and prevent its interaction with cognate antigen-major histocompatibility complex (MHC) [8], as well as by the production of arginase-1 that in combination with high levels of iNOS restricts the availability of the amino acid L-arginine, which is essential for T-cell proliferation [9]. It has been suggested that the usage of each mechanism may depend on the specific MDSC subset and the site of immunosuppression [10].…”

PI3Kγ Activates Integrin α4 and Promotes Immune Suppressive Myeloid Cell Polarization during Tumor Progression

“…[myeloid-derived suppressor cells (MDSCs)] accumulate in the blood, spleen, lymph nodes, bone marrow, and tumor microenvironments in tumor-bearing animals and cancer patients (4)(5)(6)(7)(8). These cells, as well as CD11b þ Gr1 -tissue resident macrophages, inhibit innate and adaptive immunity, thereby promoting tumor immune escape (1)(2)(3)(4)(5)(6)(7)(8).…”

“…These cells, as well as CD11b þ Gr1 -tissue resident macrophages, inhibit innate and adaptive immunity, thereby promoting tumor immune escape (1)(2)(3)(4)(5)(6)(7)(8). These immunosuppressive cells inhibit maturation of antigen-presenting dendritic cells (DCs), suppress T-cell activation and NK-cell cytotoxicity and induce regulatory T-cell (Treg) development, leading to dysfunctional cell-mediated antitumor immunity through the release of immunosuppressive factors such as IL10, TGFb1, IL6, VEGF, and ROS (9)(10).…”