Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity

Abstract Lactate is a key metabolite produced from glycolytic metabolism of glucose molecules, yet it also serves as a primary carbon fuel source for many cell types. In the tumor-immune microenvironment, effect of lactate on cancer and immune cells can be highly complex and hard to decipher, which is further confounded by acidic protons, a co-product of glycolysis. Here we show that lactate is able to increase stemness of CD8 + T cells and augments anti-tumor immunity. Subcutaneous administration of sodium lactate but not glucose to mice bearing transplanted MC38 tumors results in CD8 + T cell-dependent tumor growth inhibition. Single cell transcriptomics analysis reveals increased proportion of stem-like…

• UO
  University of Texas Southwestern Medical Center
• CH
  Children’s Hospital of Wisconsin Research Institute
• NI
  National Institutes of Health

  Awards: P01 HD087150, U01CA218422, R01CA216839
• DO
  Division of Cancer Epidemiology and Genetics, National Cancer Institute

  Awards: U01CA218422, R01CA216839