Intratumoral Microbiome: Impact on Cancer Progression and Cellular Immunotherapy

The intratumoral microbiota, comprising bacteria, fungi, and viruses within the tumor microenvironment, actively influences carcinogenesis. Key mechanisms include the induction of host DNA damage, modulation of critical oncogenic signaling pathways such as WNT-β-catenin, NF-κB, and PI3K, and the orchestration of inflammatory processes. The microbiome’s interaction with the host immune system is complex and bidirectional. On one hand, specific microbes can foster a pro-tumorigenic niche by suppressing the activity of cytotoxic T cells and natural killer (NK) cells or by promoting the accumulation of immunosuppressive cell types like tumor-associated macrophages (TAMs). On the other hand, microbial components can serve as neoantigens for T cell recognition or produce metabolites that reprogram the immune landscape to enhance anti-tumor responses. The composition of this microbiome is emerging as a crucial factor influencing the outcomes of immunotherapies. Prospective investigations in cancer immunotherapy ought to prioritize mechanistic inquiry employing integrative multi-omics methodologies. The execution of meticulously designed clinical trials for the validation of microbial biomarkers, and the systematic, evidence-based development of microbiome-targeted therapeutic interventions aimed at enhancing antitumor immune responses. © 2025 by the authors.