• Mashup Score: 1

    Abstract. The tumor microenvironment (TME) restricts anti-tumor CD8+ T cell function and immunotherapy responses. Cancer cells compromise metabolic fitness of CD8+ T cells within the TME, but the mechanisms are largely unknown. Here we demonstrate one carbon (1C) metabolism is enhanced in T cells in an antigen-specific manner. Therapeutic supplementation of 1C metabolism using formate enhances CD8+ T cell fitness and anti-tumor efficacy of PD-1 blockade in B16-OVA tumors. Formate supplementation drives transcriptional alterations in CD8+ T cell metabolism and increases gene signatures for cellular proliferation and activation. Combined formate and anti-PD-1 therapy increases tumor-infiltrating CD8+ T cells, which are essential for the enhanced tumor control. Our data demonstrate formate provides metabolic support to CD8+ T cells reinvigorated by anti-PD-1 to overcome a metabolic vulnerability in 1C metabolism in the TME to further improve T cell function.

    Tweet Tweets with this article
    • Formate Supplementation Enhances Anti-Tumor CD8+ #TCell Fitness and Efficacy of PD-1 Blockade, by Jared Rowe, @ilaria_elia, @HaigisLab, Arlene Sharpe et al. https://t.co/w0DLZUMhze @DanaFarber @harvardmed #Immunotherapy https://t.co/d1Q1vYp2eu