Abstract
The metabolic changes that occur in tumor microenvironment (TME) can influence not only the biological activity of tumor cells, which become more aggressive and auto sustained, but also the immune response against tumor cells, either producing ineffective responses or polarizing the response toward protumor activity. γδ T cells are a subset of T cells characterized by a plasticity that confers them the ability to differentiate towards different cell subsets according to the microenvironment conditions. On this basis, we here review the more recent studies focused on altered tumor metabolism and γδ T cells, considering their already known antitumor role and the possibility of manipulating their effector functions by in vitro and in vivo approaches. γδ T cells, thanks to their unique features, are themselves a valid alternative to overcome the limits associated with the use of conventional T cells, such as major histocompatibility complex (MHC) restriction, costimulatory signal and specific tumor-associated antigen recognition. Lipids, amino acids, hypoxia, prostaglandins and other metabolic changes inside the tumor microenvironment could reduce the efficacy of this important immune population and polarize γδ T cells toward IL17 producing cells that play a pro tumoral role. A deeper knowledge of this phenomenon could be helpful to formulate new immunotherapeutic approaches that target tumor metabolisms.
Highlights
Naive T cells states dictate the engagement of distinct metabolic pathways to proliferate and maintain rely on the full oxidation of glucose through oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) to effector functions
The microenvironment heterogeneity can be the bearer of changes that can damage the antitumor functions of γδ T cells, as pointed out in a study on breast cancer or hepatocellular carcinoma in which tumor-infiltrating γδ T cells correlated with the presence of IL17 and with advanced stages of cancer [23,24]
When exposed to hypoxia, γδ T cells, expanded from healthy donors and oral cancer patients, significantly reduced their cytotoxic activity against nitrogen-containing bisphosphonates (N-BPs)-treated oral cancer cell lines compared to normoxia
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. All of them necessary for tumor cell proliferation, depriving them of metabolism provides amino acids, nucleic acids and glutathione, all of them necessary for immune cells in the TME and limiting their ability to proliferate. High levels of these lipid metabolites theIn. TME steer immune produced by tumor cells promotes the of suppressive immune cells toward immunosuppressive andexpression anti-inflammatory functions [11]. Immune cells under resting or activated of distinct metabolic pathways to proliferate and maintain effector functions. Naive T cells states dictate the engagement of distinct metabolic pathways to proliferate and maintain rely on the full oxidation of glucose through OXPHOS and fatty acid oxidation (FAO) to effector functions.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
