Ionic Regulation of T-Cell Function and Anti-Tumour Immunity

• Published in: International journal of molecular sciences Vol. 22; no. 24; p. 13668
• Main Authors: Ginefra, Pierpaolo, Carrasco Hope, Helen, Spagna, Mattia, Zecchillo, Alessandra, Vannini, Nicola
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.12.2021; MDPI
• Subjects: Antigens; Cancer; Cancer therapies; Cell activation; Cytokines; Enzymes; Gene Expression Regulation, Neoplastic; Homeostasis; Humans; Immunity; immunomodulation; Immunotherapy; Ions; Ions - metabolism; Lipids; Lymphocytes; Lymphocytes T; Mammals; Melanoma; Metabolism; Metabolites; Microenvironments; Micronutrients; Minerals; Mitochondria; Neoplasms - immunology; nutrient competition; Potassium; Review; Signal Transduction; T cell; T-Lymphocytes - immunology; Tumor Microenvironment; Tumors; tumour microenvironment; Vitamins; immunomodulation; ions; tumour microenvironment; nutrient competition; T cell
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222413668

The capacity of T cells to identify and kill cancer cells has become a central pillar of immune-based cancer therapies. However, T cells are characterized by a dysfunctional state in most tumours. A major obstacle for proper T-cell function is the metabolic constraints posed by the tumour microenvironment (TME). In the TME, T cells compete with cancer cells for macronutrients (sugar, proteins, and lipid) and micronutrients (vitamins and minerals/ions). While the role of macronutrients in T-cell activation and function is well characterized, the contribution of micronutrients and especially ions in anti-tumour T-cell activities is still under investigation. Notably, ions are important for most of the signalling pathways regulating T-cell anti-tumour function. In this review, we discuss the role of six biologically relevant ions in T-cell function and in anti-tumour immunity, elucidating potential strategies to adopt to improve immunotherapy via modulation of ion metabolism.