Intratumoral microbiota—the microbial populations residing within solid tumors—have emerged as pivotal components of the tumor microenvironment (TME), influencing tumor initiation, progression, and therapeutic outcomes. In a comprehensive review published in Med Research, researchers from Southern Medical University and collaborating institutions systematically examine the heterogeneity of these microorganisms and their multifaceted roles in cancer biology.
The authors categorize microbial heterogeneity at three distinct levels: among different tumor types, within individual tumors, and between tumors and adjacent non-tumorous tissues. Tumors such as colorectal, breast, gastric, and pancreatic cancers exhibit distinct microbial profiles, with notable diversity in both species composition and spatial localization. These microbial communities may be shaped by tumor subtype, anatomical location, stage of progression, or patient-specific factors such as age, diet, or comorbidities.
Functionally, the intratumoral microbiota exert a broad spectrum of effects on the TME, ranging from immunostimulatory to immunosuppressive and from antitumor to protumor. Some microbes enhance immune surveillance and cytotoxic T cell responses, while others promote immune evasion, stromal remodeling, and metabolic reprogramming. The review also discusses how microbial metabolites and signaling pathways interface with host immune regulation and tumor cell behavior, highlighting both supportive and inhibitory roles in cancer progression. Importantly, the authors emphasize that these functional effects are context-dependent and may vary across tumor types and clinical settings.
Beyond mechanistic insights, the review underscores the methodological challenges of characterizing intratumoral microbiota, particularly in distinguishing live microbes from microbial fragments and contaminants. To address this, the authors advocate for the integration of advanced technologies—such as single-cell and spatial transcriptomics, metagenomics, and high-resolution imaging—to refine our understanding of microbial localization, viability, and host–microbe interactions at the microscale.
By summarizing emerging evidence across diverse tumor types, this work provides a conceptual framework for interpreting intratumoral microbiota as active participants in tumor biology. It also lays the groundwork for future investigations into microbiota-informed diagnostic strategies and therapeutic interventions in precision oncology.
