Lactic Acid Induces Dendritic Cell Pyroptosis through MCT-1 to Promote Tumor Immune Evasion
Introduction:Elevated lactic acid in the tumor microenvironment (TME) creates animmunosuppressive environment. Dendritic cells (DCs) play a critical role in initiatingand regulating immune responses against tumors; however, the impact of lactic acidon DC survival within the TME is not well understood.Objectives:To investigate the impact of lactic acid on DC pyroptosis and its role intumor immune evasion and progression, while elucidating the underlying mechanisms.Methods:In vitro and in vivo models were used to evaluate the effects of lactic acid onbone marrow-derived dendritic cells (BMDCs), with a focus on pyroptosis induction.Western blotting, qPCR, flow cytometry, and immunofluorescence techniques wereemployed to investigate the mechanistic pathways, particularly the role ofmonocarboxylate transporter 1 (MCT1).Results:Lactic acid induced dose-dependent pyroptosis of BMDCs via cleavage ofGSDMD. This process was mediated by MCT1-dependent signaling through theK+/NLRP3/GSDMD pathway, facilitating immune evasion and tumor progression.Furthermore, MCT1 inhibition attenuated lactic acid-induced DC pyroptosis both in vitroand in vivo, suggesting its potential as a therapeutic target.Conclusion:Our findings reveal that lactic acid induces DC pyroptosis via theMCT1/K+/NLRP3/GSDMD pathway, promoting immune escape and tumorprogression. Targeting MCT1 to attenuate DC pyroptosis presents a promisingtherapeutic strategy for cancer treatment.