While the gut microbiome is known to modulate systemic immunity and response to immune checkpoint inhibitors, the role of tumor-resident microbiota remains underexplored. Recent evidence suggests that these local microbial communities may influence intratumoral immunity and therapeutic outcomes.

A systematic review compliant with PRISMA guidelines was conducted to evaluate the impact of tumor-associated bacteria on anti-tumor immune responses. Four databases (PubMed, Scopus, Web of Science and EMBASE) were searched for studies published between January 2010 and April 2025. Eligible studies characterized non-intestinal microbiota within tumor tissue and assessed immune endpoints such as T cell infiltration, cytokine profiles, PD-L1 expression, or immune checkpoint inhibitors responsiveness. Due to endpoint heterogeneity, no meta-analysis was performed. Seventeen studies met inclusion criteria.

In tumors including melanoma, pancreatic, esophageal, gastric, breast, lung, and colorectal cancers, intratumoral bacteria modulated immune responses and immune checkpoint inhibitors efficacy. Three recurring mechanisms emerged: immune activation via antigen presentation and Th1 polarization; immune suppression through regulatory T cell recruitment and stromal remodeling; and checkpoint modulation and T cell exhaustion via microbial signaling. These effects were spatially structured and tumor-context dependent.

Tumor-local microbiota represents a distinct and actionable component of the tumor-immune microenvironment. Incorporating microbial profiling into immuno-oncology strategies may enhance biomarker discovery, patient stratification, and development of microbiome-based therapies. Further research is warranted to map spatial microbial heterogeneity, validate functional mechanisms, and translate findings into clinical applications in precision immunotherapy.