TY  - JOUR
AU  - Li, Sifan
AU  - Che, Chang
AU  - Zhou, Yelu
AU  - Fan, Daiming
AU  - Bai, Xue
AU  - Lu, Yuanyuan
AU  - Zhao, Xiaodi
PY  - 2026
TI  - Gut microecology empowers cancer immunotherapy: commensal microbiota-mediated mechanisms and translational prospects of PD-1/PD-L1 therapy
JO  - Cancer Biology & Medicine
SN  - 2095-3941
SP  - 60
EP  - 77
VL  - 23
IS  - 1
AB  - 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.
UR  - https://doi.org/10.20892/j.issn.2095-3941.2025.0347
DO  - 10.20892/j.issn.2095-3941.2025.0347