@article{Li2026, 
author = {Sifan Li and Chang Che and Yelu Zhou and Daiming Fan and Xue Bai and Yuanyuan Lu and Xiaodi Zhao},
title = {Gut microecology empowers cancer immunotherapy: commensal microbiota-mediated mechanisms and translational prospects of PD-1/PD-L1 therapy},
year = {2026},
journal = {Cancer Biology & Medicine},
volume = {23},
number = {1},
pages = {60-77},
keywords = {Gut microbiota, immune checkpoint inhibitors, commensal microbiota, PD-1/PD-L1, fecal microbiota transplantation},
url = {https://www.sciopen.com/article/10.20892/j.issn.2095-3941.2025.0347},
doi = {10.20892/j.issn.2095-3941.2025.0347},
abstract = {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.}
}