Unveiling the interplay between microbiota and PD1/PD-L1 axis in tumor immunity and immunotherapy

Microbial communities across diverse body sites critically shape host immunity and tumor responses. Within this framework, the PD-1/PD-L1 axis emerges as a central pathway governing tumor immune evasion and resistance to therapy. Recent evidence reveals that microbiota-from the gut, lungs, and elsewhere-significantly influence PD-1/PD-L1 signaling, thereby altering immune checkpoint blockade efficacy. This review synthesizes current understanding of the microbiota-PD-1/PD-L1 interplay, examining how microbial composition and metabolites impact immune cell activity, the tumor microenvironment, and immunotherapy outcomes. We detail mechanisms through which microbiota regulate PD-1/PD-L1 expression, fostering immune tolerance and tumor progression while modulating therapeutic responses. The translational potential of microbiota-targeted strategies to enhance PD-1/PD-L1 therapy and overcome resistance is discussed. Integrating microbiota modulation with existing immunotherapies offers promising avenues for precision cancer treatment. Advancing these concepts into clinical practice will require future research to establish microbiome-based interventions as transformative tools in oncology.