Enhancing CD8+ T Cell Fatty Acid Catabolism within a Metabolically Challenging Tumor Microenvironment Increases the Efficacy of Melanoma Immunotherapy.,Cancer Cell

当前位置： X-MOL 学术 › Cancer Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Enhancing CD8+ T Cell Fatty Acid Catabolism within a Metabolically Challenging Tumor Microenvironment Increases the Efficacy of Melanoma Immunotherapy.
Cancer Cell ( IF 50.3 ) Pub Date : 2017-09-11 , DOI: 10.1016/j.ccell.2017.08.004
Ying Zhang , Raj Kurupati , Ling Liu , Xiang Yang Zhou , Gao Zhang , Abeer Hudaihed , Flavia Filisio , Wynetta Giles-Davis , Xiaowei Xu , Giorgos C. Karakousis , Lynn M. Schuchter , Wei Xu , Ravi Amaravadi , Min Xiao , Norah Sadek , Clemens Krepler , Meenhard Herlyn , Gordon J. Freeman , Joshua D. Rabinowitz , Hildegund C.J. Ertl

How tumor-infiltrating T lymphocytes (TILs) adapt to the metabolic constrains within the tumor microenvironment (TME) and to what degree this affects their ability to combat tumor progression remain poorly understood. Using mouse melanoma models, we report that CD8⁺ TILs enhance peroxisome proliferator-activated receptor (PPAR)-α signaling and catabolism of fatty acids (FAs) when simultaneously subjected to hypoglycemia and hypoxia. This metabolic switch partially preserves CD8⁺ TILs' effector functions, although co-inhibitor expression increases during tumor progression regardless of CD8⁺ TILs' antigen specificity. Further promoting FA catabolism improves the CD8⁺ TILs' ability to slow tumor progression. PD-1 blockade delays tumor growth without changing TIL metabolism or functions. It synergizes with metabolic reprogramming of T cells to achieve superior antitumor efficacy and even complete cures.

更新日期：2017-09-11

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>