The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity-Immunometabolism-CSCIED科技核心评价数据库-手机版

The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity

The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity

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DOI	10.1097/IN9.0000000000000014
刊名	Immunometabolism IJ
年，卷(期)	2023, 5(1)
作者	Wetzel, Tanner J.; Erfan, Sheila C.; Ananieva, Elitsa A.,
作者单位	[Wetzel, Tanner J.; Erfan, Sheila C.; Ananieva, Elitsa A.] Des Moines Univ, Dept Biochem & Nutr, 3200 Grand Ave, Des Moines, IA 50312 USA
摘要	Challenges regarding successful immunotherapy are associated with the heterogeneity of tumors and the complex interactions within the surrounding tumor microenvironment (TME), particularly those between immune and tumor cells. Of interest, T cells receive a myriad of environmental signals to elicit differentiation to effector subtypes, which is accompanied by metabolic reprogramming needed to satisfy the high energy and biosynthetic demands of their activated state. However, T cells are subjected to immunosuppressive signals and areas of oxygen and nutrient depletion in the TME, which causes T-cell exhaustion and helps tumor cells escape immune detection. The cytosolic and mitochondrial branched chain amino transferases, BCATc and BCATm, respectively, are responsible for the first step of the branched chain amino acid (BCAA) degradation, of which, metabolites are shunted into various metabolic processes. In recent years, BCAT isoenzymes have been investigated for their role in a variety of cancers found throughout the body; however, a gap of knowledge exists regarding the role BCAT isoenzymes play within immune cells of the TME. The aim of this review is to summarize recent findings about BCAAs and their catabolism at the BCAT step during T-cell metabolic reprogramming and to discuss the BCAT putative role in the anti-tumor immunity of T cells. Not only does this review acknowledges gaps pertaining to BCAA metabolism in the TME but it also identifies the practical application of BCAA metabolism in T cells in response to cancer and spotlights a potential target for pharmacological intervention.
Abstract	Challenges regarding successful immunotherapy are associated with the heterogeneity of tumors and the complex interactions within the surrounding tumor microenvironment (TME), particularly those between immune and tumor cells. Of interest, T cells receive a myriad of environmental signals to elicit differentiation to effector subtypes, which is accompanied by metabolic reprogramming needed to satisfy the high energy and biosynthetic demands of their activated state. However, T cells are subjected to immunosuppressive signals and areas of oxygen and nutrient depletion in the TME, which causes T-cell exhaustion and helps tumor cells escape immune detection. The cytosolic and mitochondrial branched chain amino transferases, BCATc and BCATm, respectively, are responsible for the first step of the branched chain amino acid (BCAA) degradation, of which, metabolites are shunted into various metabolic processes. In recent years, BCAT isoenzymes have been investigated for their role in a variety of cancers found throughout the body; however, a gap of knowledge exists regarding the role BCAT isoenzymes play within immune cells of the TME. The aim of this review is to summarize recent findings about BCAAs and their catabolism at the BCAT step during T-cell metabolic reprogramming and to discuss the BCAT putative role in the anti-tumor immunity of T cells. Not only does this review acknowledges gaps pertaining to BCAA metabolism in the TME but it also identifies the practical application of BCAA metabolism in T cells in response to cancer and spotlights a potential target for pharmacological intervention.
关键词	BCATc; BCATm; BCAA; leucine; immunotherapy; TME
KeyWord	BCATc; BCATm; BCAA; leucine; immunotherapy; TME
基金项目
页码	1-11

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Wetzel, Tanner J.; Erfan, Sheila C.; Ananieva, Elitsa A.. The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity [J]. Immunometabolism. 2023; 5; (1). 1 - 11.

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