期刊
IMMUNOTHERAPY
卷 11, 期 4, 页码 335-345出版社
FUTURE MEDICINE LTD
DOI: 10.2217/imt-2018-0141
关键词
cancer therapy; CAR T cells; hypoxia; metabolism; Tcell engineering; Tcell exhaustion; tumor microenvironment
类别
资金
- Cancerfonden [4-251/2017]
- Dr Ake Olsson Foundation
- Radiumhemmet
- Mix
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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