Gut microecology empowers cancer immunotherapy:commensal microbiota-mediated mechanisms and translational prospects of PD-1/PD-L1 therapyOA
Anti-programmed cell death protein 1(PD-1)or its ligand(PD-L1)are immune checkpoint inhibitors(ICIs)that have revolutionized cancer therapy.However,the efficacy of anti-PD-1 and anti-PD-L1 is limited by resistance and inter-individual variability.In recent years increasing evidence has highlighted the pivotal role of the gut microbiota in modulating the response to PD-1/PD-L1 immunotherapy.Extensive preclinical studies have demonstrated that commensal microbes can increase the efficacy of PD-1/PD-L1 blockade through multiple mechanisms,including the production of metabolites,such as short-chain fatty acids(SCFAs),tryptophan derivatives,and extracellular polysaccharides that remodel the tumor microenvironment,as well as the activation of immune pathways involving dendritic cells,CD8+T cells,and M1 macrophages to increase antitumor immunity.Moreover,clinical studies have shown that fecal microbiota transplantation(FMT)and targeted probiotic interventions show promise for improving the response to PD-1/PD-L1 therapy,while reducing the risk of immune-related adverse events(irAEs).This review systematically explores the multifaceted regulatory roles of the commensal microbiota in PD-1/PD-L1 therapy and examines the preclinical prospects of microbiota-based personalized immunotherapeutic strategies.The integration of multiomics technologies,synthetic biology,and precise microbiota interventions may further optimize PD-1/PD-L1 immunotherapy and offer novel insights into antitumor immune modulation.
Sifan Li;Chang Che;Yelu Zhou;Daiming Fan;Xue Bai;Yuanyuan Lu;Xiaodi Zhao
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases,Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi’an 710032,ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases,Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi’an 710032,ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases,Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi’an 710032,ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases,Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi’an 710032,ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases,Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi’an 710032,ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases,Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi’an 710032,ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases,Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi’an 710032,China
医药卫生
Gut microbiotaimmune checkpoint inhibitorscommensal microbiotaPD-1/PD-L1fecal microbiota transplantation
《Cancer Biology & Medicine》 2026 (1)
P.60-77,18
supported by grants from the National Natural Science Foundation of China(Grant Nos.82222058,82425046,and 82273142).
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