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Microbiome Modulation in Lung Cancer Immunotherapy: Unveiling the Role of Respiratory and Gut Microbiota in the PD-1/PD-L1 Response
Yuanyuan Xu (Shanghai Jiao Tong University, Shanghai Chest Hospital), Yixing Tao (Shanghai Jiao Tong University, Shanghai Chest Hospital), Hanbo Pan (Shanghai Jiao Tong University, Shanghai Chest Hospital), Zhongjie Wang (Shanghai Jiao Tong University, Shanghai Chest Hospital), Hui Wang (Shanghai Jiao Tong University, Shanghai Chest Hospital), Qingquan Luo (Shanghai Jiao Tong University, Shanghai Chest Hospital)
Abstract: Lung cancer, the leading cause of cancer-related mortality worldwide, poses considerable therapeutic challenges due to the varied responses to programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. Emerging highlight the pivotal role of host-microbiome interactions in modulating antitumor immunity and influencing clinical outcomes. This review examines how the respiratory and gut microbiota contribute to the immunosuppressive tumor microenvironment through dysbiosis-induced T-cell exhaustion and regulatory cell activation, while certain commensals facilitate dendritic cell-mediated recruitment of cytotoxic T lymphocytes. Additionally, this review explores the molecular mechanisms by which microbial metabolites, such as short-chain fatty acids, influence myeloid-derived suppressor cells. Therapeutically, microbiota-modulation strategies-such as tailored probiotic formulations and precision fecal microbiota transplantation-offer potential to enhance immunotherapy efficacy. This review provides a foundation for microbiome-guided immunotherapy, advocating for biomarker-driven patient stratification and the use of engineered microbial consortia to counteract therapeutic resistance. These findings pave the way for the integration of microbiome science into next-generation precision oncology.