Myeloid-derived suppressor cells and proinflammatory cytokines as targets for cancer therapy

Abstract

Myeloid-derived suppressor cells represent a heterogeneous population of immature myeloid cells. Under normal conditions, these cells differentiate into macrophages, dendritic cells, and granulocytes. However, in pathological states such as inflammation, infection, or tumor growth, there is an arrest of their differentiation that results in the accumulation of immature myeloid cells in the organism. In addition, these cells acquire a suppressor phenotype, expressing anti-inflammatory cytokines and reactive oxygen and nitrogen species, and suppress T-cell immune response. Myeloid-derived suppressor cells (MDSC) contribute to cancerogenesis by forming a favorable microenvironment for tumor growth. Proinflammatory cytokines, secreted by tumor cells and the tumor microenvironment, induce angiogenesis and metastasis and promote tumor growth. They also provide signals necessary for survival, accumulation, and function of MDSC. Understanding the mechanisms of myeloid suppressor cell development and the use of proinflammatory cytokine inhibitors may prove beneficial for tumor therapy.

The paradoxical role of tumor-infiltrating immune cells in lung cancer

“…MDSCs were first identified as immunosuppressive CD11b + Gr-1 + myeloid cells in cancer patients in the 1980s (38). MDSCs represent a heterogenic population of immature myeloid cells that consists of myeloid progenitors and precursors of macrophages, granulocytes, and DCs they are characterized by a potent ability to suppress various T cell functions (39).…”

CD33+ HLA-DR– Myeloid-Derived Suppressor Cells Are Increased in Frequency in the Peripheral Blood of Type1 Diabetes Patients with Predominance of CD14+ Subset

“…Under normal conditions, they differentiate into dendritic cells, macrophages and granulocytes. However, in pathological states such as infection, inflammation or cancer, there is an arrest of differentiation of this population of cells resulting in their accumulation [ 8 ][ 9 ][ 10 ]. The composition and percentage of MDSCs were found to vary according to disease nature.…”

Diamonds in the Rough: Harnessing Tumor-Associated Myeloid Cells for Cancer Therapy

“…The tumor-promoting functions comprise (i) remodeling of the TME ( 196 ), (ii) induction of (lymph)angiogenesis ( 196 ), (iii) promotion of metastasis ( 197 ), (iv) inhibition of cellular senescence ( 198 ), (v) suppression of T-cell function and migration ( 199 , 200 ) and (vi) resistance to chemo-and immunotherapy ( 201 – 203 ). It is important to note that the immunosuppressive activity of MDSCs is not limited to a single mechanism, with MDSCs engaging several mechanisms throughout the progression of the tumor ( 6 , 204 – 206 ), including; (i) expansion of Tregs ( 207 ), (ii) expression of galectin-9 on the MDSC surface, resulting in T-cell apoptosis ( 208 ), (iii) inhibition of NK cells through membrane-bound TGFβ1 ( 209 ), (iv) the secretion of ROS [ , H 2 O 2 and peroxynitrite (OONO − )]( 210 , 211 ), (v) expression of enzymes involved in amino acid catabolism, like Arginase-I and IDO, collectively inhibiting T-cell proliferation ( 212 , 213 ), and (vi) secretion of S100A8 and S100A9, resulting in the recruitment of more MDSCs and inhibition of dendritic cell maturation ( 214 , 215 ).…”