靶向树突状细胞代谢重编程:肿瘤免疫治疗新策略OA

Dendritic cells(DCs)serve as the central hub connecting innate immunity and adaptive immunity,and their functional homeostasis is critical for mediating tumor immune surveillance.However,the tumor microenvironment(TME)drives metabolic reprogramming in DCs through competition for nutrients and accumulation of immunosuppressive metabolites,thereby inducing defects in antitumor immune responses.This article systematically reviews the remodeling mechanisms of DC subsets across three major metabolic dimensions in the TME:in glucose metabolism,lactate-rich microenvironments suppress MHC class Ⅱ molecule expression via GPR81 signaling,impairing the antigen-presenting capacity of conventional DCs(cDCs);in lipid metabolism,fatty acid oxidation mediated by the Wnt5a-β-catenin-PPARγ-CPT1A axis promotes the polarization of cDCs toward an immunosuppressive phenotype;and in amino acid metabolism,cascade activation of the Arg1-IDO1 pathway induces DCs to acquire a tolerogenic phenotype.In response to these metabolic abnormalities,current intervention strategies have expanded from single-target modulation to multimodal combination approaches,including lipid nanoparticle-based in situ vaccines and mRNA delivery systems,metabolic-immune synergistic blockade,and metabolically optimized DC vaccines.Therefore,deepening the understanding and targeting of DC metabolic checkpoints not only holds promise for reversing the immunosuppressive microenvironment and overcoming therapeutic resistance,but also provides important scientific rationale and translational strategies for developing next-generation metabolic-immune combination therapies.