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Metabolic regulation of CAR T cell function by the hypoxic microenvironment in solid tumors

Research output: Contribution to journalReview article

Anna Schurich, Isabelle Magalhaes, Jonas Mattsson

Original languageEnglish
Pages (from-to)335-345
Number of pages11
JournalImmunotherapy
Volume11
Issue number4
DOIs
Publication statusPublished - 1 Mar 2019

King's Authors

Abstract

The field of immunometabolism has attracted growing attention as an area at the heart of immune regulation. Upon activation, T cells undergo significant metabolic changes allowing them to mediate effector responses. The advent of chimeric antigen receptor T cell-adoptive therapy has shown some striking clinical efficacy but fails to induce sufficient antitumor response in many patients. Solid tumors put up significant opposition creating a microenvironment deficient of oxygen and glucose, depriving T cells of energy and pushing them to exhaustion. Here, we focus on immune suppressive mechanisms related to hypoxia in the tumor microenvironment and the resulting metabolic changes in T cells. New therapeutic approaches such as generating chimeric antigen receptor T cells able to withstand the challenging solid tumor microenvironment are needed.

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