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    Enhancing CD8T Cell Fatty Acid Catabolism within a Metabolically Challenging Tumor Microenvironment Increases the Efficacy of Melanoma Immunotherapy.

    Cancer Cell 2017 Sep;32(3):377-391.e9
    The Wistar Institute, Philadelphia, PA 19104, USA. Electronic address:
    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 CD8TILs 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 CD8TILs' effector functions, although co-inhibitor expression increases during tumor progression regardless of CD8TILs' antigen specificity. Further promoting FA catabolism improves the CD8TILs' 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.
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    http://dx.doi.org/10.1016/j.ccell.2017.08.004DOI ListingPossible
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751418PMCFound

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