Intra-tumor microbiome-based tumor survival indices predict immune interaction and drug sensitivity on pan-cancer scale.

Growing research evidence indicates a substantial influence of the intra-tumor microbiome on tumor outcome. However, there is currently no consistent criterion for identifying the association of microbes with tumor progression and response to treatment across various types of cancer. In this study, we concentrate on the intra-tumor microbiome and develop the Tumor Microbiome Survival Index (TMSI), a measure indicative of cancer patient survival risk. Our indices revealed notable distinctions between two stratified risk groups for each of the 10 cancer types and could precisely predict patients' overall survival. For each type of cancer, our findings unveiled two distinct gene expression profiles and shed light on the varying patterns of immune and stromal cell enrichment between the two risk groups. Additionally, we noted that the high-TMSI group exhibited substantially elevated IC50 values for a number of drugs, indicating that individuals in the low-TMSI group might experience superior therapeutic effects from chemotherapy. These findings illuminate the complex dynamics between the tumor microbiome, the patient's immune reaction, and medical outcomes, thus shedding light on microbiome-based personalized therapeutic interventions. IMPORTANCE: This work presents the Tumor Microbiome Survival Index (TMSI), a crucial innovation. It stratifies cancer patients into risk groups across 10 cancer types, accurately predicting survival. By uncovering distinct gene expression and immune/stromal cell patterns, it deepens understanding of tumor complexity. The finding of altered drug sensitivity in different TMSI groups offers insights for personalized chemotherapy. Overall, it paves the way for microbiome-targeted cancer therapies and enhanced patient prognostication.