Intratumoral microbiota: bidirectional modulation of tumor radiosensitivity

The term "intratumoral microbiota" refers to the microbial communities that reside within tumor tissues, including bacteria, fungi, mycoplasma, and viruses. Accumulating evidence indicates that the intratumoral microbiota is closely associated with tumor initiation and progression. Nevertheless, the impact of these microbes on radiotherapy outcomes remains largely unexplored. In this review, we discussed how the intratumoral microbiota influences radiation response, highlighting the diverse mechanisms through which microbial communities modulate tumor cell behavior. Specifically, intratumoral microbes may confer radioresistance by enhancing DNA damage repair, reprogramming core metabolic pathways, regulating the cell cycle, and modulating autophagy, thereby diminishing radiotherapy efficacy. Conversely, certain microorganisms can enhance radiosensitivity by directly inducing DNA damage in host tumor cells, activating antitumor immune responses, or elevating intracellular reactive oxygen species(ROS) levels, thereby amplifying radiation-induced cytotoxicity. Additionally, microbial aggravation of tumor hypoxia may further diminish radiosensitivity by creating a more radioresistant tumor microenvironment. Therefore, the regulatory role of the intratumoral microbiota in radiotherapy sensitivity provides a novel direction for cancer therapy. Strategies that precisely target the intratumoral microbiota hold promise as important approaches for overcoming radioresistance and improving treatment outcomes in patients with cancer.