Longevity & AgingSIRT7 Controls T Cell Cancer-Fighting Power via Amino Acid and Fat Metabolism
Researchers discovered that SIRT7, a mitochondria-associated enzyme, governs T cell antitumor function by regulating branched-chain amino acid (BCAA) catabolism and fatty acid synthesis. In mice lacking SIRT7 specifically in T cells, BCAA metabolites and fatty acids accumulate, reducing cytotoxic cytokine output (notably IFN-γ) and accelerating T cell exhaustion. Mechanistically, SIRT7 desuccinylates key BCAA catabolic enzymes, keeping their activity in check. Inhibiting BCAA catabolism pharmacologically or removing dietary BCAAs rescued T cell function, while adding fatty acids worsened it. These findings position SIRT7 as a metabolic checkpoint linking nutrient sensing to cancer immunity.
