Microbiome-guided cancer immunotherapy: immune mechanisms, resistance pathways, and translational opportunities for...

The gut microbiome is increasingly recognized as a modulator of tumor-immune interactions and has been associated with cancer development, progression, and therapeutic response, while direct causal evidence remains strongest in mechanistic and interventional models. Microbial composition and metabolites, including SCFAs, bile acids, inosine, and tryptophan-derived products, may shape host immunity by influencing the tumor microenvironment (TME) and systemic immune responses, although the strength of evidence varies by model system and clinical context. These microbial signals have been linked to changes in T cells, B cells, NK cells, and MDSCs, with mechanistic studies supporting effects on cytokine networks, immune checkpoint signaling, inflammation, and antitumor immunity. Emerging translational evidence indicates that specific microbial signatures may serve as predictive biomarkers for immunotherapy efficacy, resistance, and treatment-related toxicity. In parallel, microbiome-targeted strategies, including FMT, probiotics, prebiotics, dietary modulation, and engineered microbial therapeutics, are being investigated as adjunctive approaches to improve cancer therapy, but their clinical efficacy remains incompletely validated. Understanding microbiome-immune crosstalk may therefore support precision oncology by identifying tractable microbial targets for improving therapeutic outcomes, overcoming immune-mediated treatment resistance, and guiding patient stratification across diverse cancer types and settings in clinical oncology practice.