Gut microbiota affects PD-L1 therapy and its mechanism in melanoma

Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 blockade, have shown great success in treating melanoma. PD-L1 (B7-H1, CD274), a ligand of PD-1, binds to PD-1 on T cells, inhibiting their activation and proliferation through multiple pathways, thus dampening tumor-reactive T cell activity. Studies have linked PD-L1 expression in melanoma with tumor growth, invasion, and metastasis, making the PD-1/PD-L1 pathway a critical target in melanoma therapy. However, immune-related adverse events are common, reducing the effectiveness of anti-PD-L1 treatments. Recent evidence suggests that the gut microbiome significantly influences anti-tumor immunity, with the microbiome potentially reprogramming the tumor microenvironment and overcoming resistance to anti-PD-1 therapies in melanoma patients. This review explores the mechanisms of PD-1/PD-L1 in melanoma and examines how gut microbiota and its metabolites may help address resistance to anti-PD-1 therapy, offering new insights for improving melanoma treatment strategies.