Sodium Lactate Enhances Anti-Tumor Immunity!
Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity
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 TCF-1-expressing CD8+ T cells among intra-tumoral CD3+ cells, a phenotype validated by in vitro lactate treatment of T cells. Mechanistically, lactate inhibits histone deacetylase activity, which results in increased acetylation at H3K27 of the Tcf7 super enhancer locus, leading to increased Tcf7 gene expression. CD8+ T cells in vitro pre-treated with lactate efficiently inhibit tumor growth upon adoptive transfer to tumor-bearing mice. Our results provide evidence for an intrinsic role of lactate in anti-tumor immunity independent of the pH-dependent effect of lactic acid, and might advance cancer immune therapy.
Lactate Inhibits Tumor Growth in Mice
This chemical has helpful and harmful effects.
Lactate may seem an unlikely anti-cancer drug candidate since lactic acid actually helps tumor evade immune defenses. However, this intriguing study shows that when taken out of the context of tumor acidity, sodium lactate can significantly impede, and even revert, tumor growth, especially when combined with some existing anti-cancer medications – a new paradigm that probably deserves additional research. One of its obvious advantages is the ability to induce the stem-like phenotype in T cells in vitro. The researchers suggest that sodium lactate can be used that way to increase the effectiveness of CAR-T cell therapy.
 Feng, Q., Liu, Z., Yu, X. et al. Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity. Nat Commun 13, 4981 (2022).
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