How the Potassium Channel Response of T Lymphocytes to the Tumor Microenvironment Shapes Antitumor Immunity

• Published in: Cancers Vol. 14; no. 15; p. 3564
• Main Authors: Chirra, Martina, Newton, Hannah S., Gawali, Vaibhavkumar S., Wise-Draper, Trisha M., Chimote, Ameet A., Conforti, Laura
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 22-07-2022; MDPI
• Subjects: Antigen presentation; Apoptosis; Calcium channels; Calcium influx; Cancer; Cell cycle; Cell death; Cell proliferation; Cytokines; Cytotoxicity; Effector cells; Genotype & phenotype; Homeostasis; Hypoxia; Immune system; Immunity; Immunotherapy; Ion channels; Lymphocytes; Lymphocytes T; Metabolism; Motility; Plasma; Potassium; Review; Reviews; T cell receptors; Transcription factors; Tumor cells; Tumor microenvironment; Tumor necrosis factor-TNF; Tumors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14153564

Competent antitumor immune cells are fundamental for tumor surveillance and combating active cancers. Once established, tumors generate a tumor microenvironment (TME) consisting of complex cellular and metabolic elements that serve to suppress the function of antitumor immune cells. T lymphocytes are key cellular elements of the TME. In this review, we explore the role of ion channels, particularly K+ channels, in mediating the suppressive effects of the TME on T cells. First, we will review the complex network of ion channels that mediate Ca2+ influx and control effector functions in T cells. Then, we will discuss how multiple features of the TME influence the antitumor capabilities of T cells via ion channels. We will focus on hypoxia, adenosine, and ionic imbalances in the TME, as well as overexpression of programmed cell death ligand 1 by cancer cells that either suppress K+ channels in T cells and/or benefit from regulating these channels’ activity, ultimately shaping the immune response. Finally, we will review some of the cancer treatment implications related to ion channels. A better understanding of the effects of the TME on ion channels in T lymphocytes could promote the development of more effective immunotherapies, especially for resistant solid malignancies.