Intratumoral Microbiota in Tumor: Current Understandings and Future Perspectives

Intratumoral bacteria are increasingly recognized as integral and dynamic components of the tumor microenvironment (TME), with profound implications for tumor initiation, progression, metastasis, immune remodeling, and therapeutic response. These microorganisms may originate from mucosal barrier breaches, hematogenous or lymphatic dissemination, local migration from adjacent tissues, or co-migration with metastatic cells, and can be characterized by sequencing-based, imaging, culture-dependent, and multi-omics approaches. Accumulating evidence indicates that intratumoral bacteria contribute to tumorigenesis by inducing genomic instability, DNA damage, epigenetic alterations, oncogenic signaling, and chronic inflammation. Beyond primary tumor growth, they participate in multiple steps of the metastatic cascade, including epithelial-mesenchymal transition, cytoskeletal remodeling, invasion, intravasation, extravasation, pre-metastatic niche formation, angiogenesis, and distant colonization. Intratumoral bacteria also reshape immune and non-immune compartments of the TME, exerting dual effects by promoting immune suppression or enhancing antitumor immunity depending on bacterial species, tumor context, and host immune status. In this review, we summarize the historical development, methodological advances, cancer-type-specific diversity, and mechanistic roles of intratumoral microbiota in tumor progression and metastasis. We further discuss their diagnostic and prognostic value, as well as their therapeutic implications for conventional anticancer treatments and microbiota-targeted strategies, highlighting opportunities and challenges for microbiota-guided precision oncology.