Myeloid-Derived Suppressor Cells: Ductile Targets in Disease

Abstract

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells with major regulatory functions and rise during pathological conditions, including cancer, infections and autoimmune conditions. MDSC expansion is generally linked to inflammatory processes that emerge in response to stable immunological stress, which alter both magnitude and quality of the myelopoietic output. Inability to reinstate physiological myelopoiesis would fall in an “emergency state” that perpetually reprograms myeloid cells toward suppressive functions. While differentiation and reprogramming of myeloid cells toward an immunosuppressive phenotype can be considered the result of a multistep process that originates in the bone marrow and culminates in the tumor microenvironment, the identification of its driving events may offer potential therapeutic approaches in different pathologies. Indeed, whereas expansion of MDSCs, in both murine and human tumor bearers, results in reduced immune surveillance and antitumor cytotoxicity, placing an obstacle to the effectiveness of anticancer therapies, adoptive transfer of MDSCs has shown therapeutic benefits in autoimmune disorders. Here, we describe relevant mechanisms of myeloid cell reprogramming leading to generation of suppressive MDSCs and discuss their therapeutic ductility in disease.

Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities

“…These cells are now known as MDSCs, a heterogeneous population of immature myeloid cell. MDSCs are also plastic and respond to microenvironment signals [40][41][42]. MDSCs can differentiate into macrophages, granulocytes and dendritic cells (DCs) in vitro.…”

“…It has been reported that the immunosuppressive activity of MDSCs in the tumor microenvironment mainly includes (a) inducing differentiation and expansion of Tregs; (b) inhibiting the polarization of DCs, NKs and macrophages to the M2 phenotype; (c) depriving T cells of essential amino acids; (d) inducing oxidative stress ( Fig. 2) [40][41][42][43]. We mainly reviewed the MDSCs in the tumor growth, angiogenesis, and metastasis of HCC in this context (Table 1) and an increase in immunosuppressive cytokine levels in HCC patients, revealing the potential mechanistic network for immune disorders in HCC patients compared with the normal control group [55].…”

Dynamic alterations of myeloid-derived suppressor cells and CD68+CD163+M2-like macrophages of non-small cell lung cancer patients in radiotherapy

“…MDSCs expansion are generally linked to in ammatory processes [32]. Recent studies showed that MDSCs could expand under pathological conditions including multiple sclerosis [33], 1 diabetes [34], rheumatoid arthritis [35], systemic lupus erythematosus [36], and autoimmune hepatitis [37].…”

Use of STAT6 Phosphorylation Inhibitor and Trimethylglycine as New Adjuvant Therapies for 5-Fluorouracil in Colitis-Associated Tumorigenesis

“…Myeloid and lymphoid circulating cells were analyzed by flow cytometry. An increase in myeloid monocytic cells in peripheral blood has been associated with some inflammatory pathologies [36]. In particular, CD11b+Ly6C hi (Ly6C hi ) monocytes increase in number during intestinal inflammation associated with tumor growth and invasiveness [37].…”