A lactate–α-ketoglutarate metabolic circuit in tumor-infiltrating regulatory T cells accelerates tumor progression by inducing NK cell senescence

A lactate–α-ketoglutarate metabolic circuit operating in tumor-infiltrating regulatory T cells drives WNT2-mediated senescence-like changes in natural killer cells, thereby accelerating tumor progression. Shi et al. demonstrated that disrupting this metabolic axis restores NK cell function and hinders tumor growth. The findings reveal a previously unknown immunosuppressive mechanism in the tumor microenvironment and identify potential therapeutic targets to reinvigorate anti-tumor innate immunity.