Regulation of T Cells in Cancer by Nitric Oxide

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 10; p. 2655
• Main Authors: Navasardyan, Inesa, Bonavida, Benjamin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05-10-2021; MDPI
• Subjects: Animals; Antibodies; Antigens; Cancer; CD4 antigen; CD8 antigen; Cell activation; Cell death; Cell differentiation; Cytokines; Cytotoxicity; Death receptors; Effector cells; Helper cells; Humans; Immune response (cell-mediated); Immune system; immunotherapy; Infectious diseases; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Neoplasms - immunology; Neutrophils; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitric-oxide synthase; Peptides; Regulation; Review; Suppressor cells; T cell; T cell receptors; T-Lymphocytes - immunology; Tumor microenvironment; Tumor Microenvironment - immunology; Tumor necrosis factor-TNF; nitric oxide; cancer; nitric oxide synthase; T cell; immunotherapy
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10102655

The T cell-mediated immune response is primarily involved in the fight against infectious diseases and cancer and its underlying mechanisms are complex. The anti-tumor T cell response is regulated by various T cell subsets and other cells and tissues in the tumor microenvironment (TME). Various mechanisms are involved in the regulation of these various effector cells. One mechanism is the iNOS/.NO that has been reported to be intimately involved in the regulation and differentiation of the various cells that regulate the anti-tumor CD8 T cells. Both endogenous and exogenous .NO are implicated in this regulation. Importantly, the exposure of T cells to .NO had different effects on the immune response, depending on the .NO concentration and time of exposure. For instance, iNOS in T cells regulates activation-induced cell death and inhibits Treg induction. Effector CD8 T cells exposed to .NO result in the upregulation of death receptors and enhance their anti-tumor cytotoxic activity. .NO-Tregs suppress CD4 Th17 cells and their differentiation. Myeloid-derived suppressor cells (MDSCs) expressing iNOS inhibit T cell functions via .NO and inhibit anti-tumor CD8 T cells. Therefore, both .NO donors and .NO inhibitors are potential therapeutics tailored to specific target cells that regulate the T cell effector anti-tumor response.