Lactic acid induces dendritic cell pyroptosis through MCT-1 to promote tumor immune evasion

Elevated metabolites in the tumor microenvironment (TME), particularly lactic acid, create an immunosuppressive milieu that promotes immune escape and tumor progression. Dendritic cells (DCs) are pivotal in initiating and regulating immune responses against tumors. However, the impact of lactic acid on DC death in the TME remains unclear. Our study reveals that lactic acid induces dose-dependent pyroptosis of bone marrow-derived DCs (BMDCs) through GSDMD cleavage. Mechanistically, this process involves monocarboxylate transporter 1(MCT1)-mediated signaling via the K⁺/NLRP3/GSDMD axis, facilitating immune evasion and cancer progression. Furthermore, inhibiting MCT1 attenuated lactic acid-induced DC pyroptosis both in vitro and in vivo. These findings offer mechanistic insights into how lactic acid-mediated DC pyroptosis contributes to tumor immune evasion, suggesting potential targets for enhancing cancer therapies.