Fundamentals of T Cell Metabolism and Strategies to Enhance Cancer Immunotherapy

• Type of Material: Article
• Authors: Guillermo O Rangel Rivera, Medical University of South Carolina; Hannah M Knochelmann, Medical University of South Carolina; Connor J Dwyer, Medical University of South Carolina; Aubrey S Smith, Medical University of South Carolina; Megan M Wyatt, Emory University; Amalia M Rivera-Reyes, Emory University; Jessica E Thaxton, Medical University of South Carolina; Chrystal Paulos, Emory University
• Language: English
• Date: 2021-03-18
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Rangel Rivera, Knochelmann, Dwyer, Smith, Wyatt, Rivera-Reyes, Thaxton and Paulos
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fimmu.2021.645242
• Title of Journal or Parent Work: FRONTIERS IN IMMUNOLOGY
• Volume: 12
• Start Page: 645242
• End Page: 645242
• Grant/Funding Information: This work was supported by the NIH Training grant T32 5T32GM008716-19 and MUSC CGS Provost Scholarship to GR. NIH Training grant T32 GM08716 and NCI F30 243307 to HK. NIH training grant T32 AI132164-01 to CD. Hollings Cancer Center Graduate Fellowship to AS. NIH R50 CA233186 to MW. NIH R01 CA175061 and R01 CA208514 grants, KL2 South Carolina Clinical and Translational Research grant UL1 TR000062, ACS-IRG grant 016623-004 and MUSC Start-up funds to CP.
• Keywords: CHEMOTHERAPY; MITOCHONDRIAL DYNAMICS; immune checkpoint therapy; tumor microenvironment; LYMPHOCYTES; Science & Technology; LIPOLYSIS; Immunology; adoptive T cell transfer; GLUCOSE; tumor infiltrating lymphocytes; MODULATION; REGULATOR; TRIGGERS; Life Sciences & Biomedicine; T cell metabolism; GLYCOLYSIS; NAIVE; tumor metabolism
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery; Biology, Microbiology

Abstract

Emerging reports show that metabolic pathways can be targeted to enhance T cell-mediated immunity to tumors. Yet, tumors consume key metabolites in the host to survive, thus robbing T cells of these nutrients to function and thrive. T cells are often deprived of basic building blocks for energy in the tumor, including glucose and amino acids needed to proliferate or produce cytotoxic molecules against tumors. Immunosuppressive molecules in the host further compromise the lytic capacity of T cells. Moreover, checkpoint receptors inhibit T cell responses by impairing their bioenergetic potential within tumors. In this review, we discuss the fundamental metabolic pathways involved in T cell activation, differentiation and response against tumors. We then address ways to target metabolic pathways to improve the next generation of immunotherapies for cancer patients.