Decoding the Immuno-Oncology-Microbiome axis: Breakthroughs in mechanisms, technologies, and clinical applications

Abstract

The Immuno-Oncology-Microbiome (IOM) axis is a tripartite regulatory system involving microbiota, immune cells, and tumors, which critically modulates cancer progression and therapy response. This systematic review synthesizes key advances from 2022 to 2025, illustrating the field’s evolution from macro-associations to precise molecular mechanisms, driven by innovations in single-cell multi-omics, spatial biology, and synthetic biology. Mechanistically, the IOM axis functions via bidirectional pathways: immunostimulatory effects are mediated by microbial metabolites and components that sensitize tumors to immunotherapy, while immunosuppression is induced by pathobionts that remodel the tumor microenvironment to promote immune evasion and chemoresistance. Technologically, high-resolution tools have replaced traditional sequencing, enabling host-microbe transcriptomics, microbial microniche mapping, and the development of engineered bacterial therapeutics. Cancer-specific IOM signatures reveal organ-axis specialization, with distinct immune crosstalk patterns in colorectal cancer, melanoma, and hepatocellular carcinoma. Translational advances include standardized fecal microbiota transplantation, cancer-type specific probiotics/postbiotics, and engineered bacterial platforms, alongside microbial biomarkers for predicting therapy response. Despite progress, bottlenecks such as technical inconsistency, high costs, inter-individual heterogeneity, and understudied low-abundance taxa remain. Future priorities focus on low-cost spatial technologies, strain-level mechanistic resolution, and standardized clinical implementation, positioning microecological therapies as integral to precision oncology.