@article{2487,
  keywords = {Animals, Glucose, Female, Humans, Treatment Outcome, Stress, Physiological, Mice, Inbred C57BL, Fatty Acids, Disease Progression, Antigens, CD, Gene Knockdown Techniques, Lymphocytes, Tumor-Infiltrating, Cell Hypoxia, Lymphocyte Activation, CD8-Positive T-Lymphocytes, Hypoxia-Inducible Factor 1, alpha Subunit, Immunotherapy, Melanoma, Oxygen, Programmed Cell Death 1 Receptor, Tumor Microenvironment},
  author = {Ying Zhang and Raj Kurupati and Ling Liu and Xiang Zhou and Gao Zhang and Abeer Hudaihed and Flavia Filisio and Wynetta Giles-Davis and Xiaowei Xu and Giorgos Karakousis and Lynn Schuchter and Wei Xu and Ravi Amaravadi and Min Xiao and Norah Sadek and Clemens Krepler and Meenhard Herlyn and Gordon Freeman and Joshua Rabinowitz and Hildegund Ertl},
  title = {Enhancing CD8(+) T Cell Fatty Acid Catabolism within~a Metabolically Challenging Tumor Microenvironment Increases the Efficacy of Melanoma Immunotherapy.},
  abstract = {<p>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\&$\#$39; effector functions, although co-inhibitor expression increases during tumor progression regardless of CD8(+) TILs\&$\#$39; antigen specificity. Further promoting FA catabolism improves the CD8(+) TILs\&$\#$39; ability to slow tumor progression. PD-1 blockade delays tumor growth without changing TIL metabolism or functions. It synergizes with metabolic reprogramming of T\&nbsp;cells to achieve superior antitumor efficacy and even complete cures.</p>
},
  year = {2017},
  journal = {Cancer Cell},
  volume = {32},
  pages = {377-391.e9},
  month = {09/2017},
  issn = {1878-3686},
  doi = {10.1016/j.ccell.2017.08.004},
  language = {eng},
}