Intratumoral microbiota and their emerging role in the tumor microenvironment

Intratumoral microbiota, as an important component of the tumor microenvironment, have attracted increasing attention in recent years for their roles in tumor initiation, progression, and therapeutic regulation. Accumulating evidence indicates that low-abundance yet relatively stable microbial communities are present in a variety of solid tumors, exhibiting marked tumor-type specificity and spatial heterogeneity. Current studies suggest that intratumoral microorganisms contribute to tumor progression through multiple mechanisms, including activation of oncogenic signaling pathways, modulation of chronic inflammatory responses, remodeling of the immunosuppressive microenvironment, and regulation of metabolic reprogramming and drug responsiveness. Meanwhile, their bidirectional effects on chemotherapy, radiotherapy, targeted therapy, and immunotherapy highlight their potential roles in determining therapeutic sensitivity and the development of resistance. Despite existing challenges such as low microbial biomass, contamination control, and difficulties in functional validation, advances in spatial multi-omics and single-cell technologies are continuously enhancing the potential clinical value of intratumoral microbiota in tumor diagnosis, prognostic assessment, and precision therapy. This review summarizes the sources, colonization mechanisms, biological functions, roles in therapeutic modulation, and clinical applications of intratumoral microbiota, aiming to provide a theoretical basis for future research and clinical translation.