Intratumoral Microorganisms in Tumors: Current Understanding and Emerging Therapeutic Strategies

Abstract

Recent advances in high-throughput sequencing, spatial omics, and integrative multiomics analyses have established reproducibly detectable microbial communities within tumor tissues, leading to the conceptualization of tumors as complex ecosystems encompassing an “intratumoral microbiota.” These microorganisms have increasingly been recognized as contributing to tumorigenesis, progression, and therapeutic response through interactions with the immune system, immunometabolic reprogramming of tissues, chronic inflammation, and genomic instability. Nevertheless, current evidence remains piecemeal and descriptive, with limited systematic consolidation of microbial composition, functional mechanisms, and translation to clinical application, particularly across tumor types and microenvironmental contexts. This review summarizes microbial diversity, tumor-type-specific associations, and multilayered mechanisms including immune modulation, metabolic reprogramming, and signaling rewiring, and discusses emerging applications such as biomarker discovery, prognostic stratification, and microbiome-targeted therapeutics. Special focus is placed on tumor microenvironment, microbiota-derived metabolites, and determinants of immunotherapy responsiveness. Overall, this review underscores the intratumoral microbiota as a dynamic and context-dependent regulatory layer in cancer biology and offers an integrated framework to realize microbiome-informed precision oncology, along with avenues for enhanced patient stratification and personalized therapeutic approaches.

Keywords

determinants of immunotherapy responsiveness / intratumoral microbiota / microbial regulation of antitumor immunity / microbiota-derived metabolites / microbiome-targeted therapeutic strategies / tumor microenvironment

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