Exploring the Key Role of Nanotechnology on Intratumoral Microbiome Modulation for Cancer Immunotherapy

ABSTRACT The intratumoral microbiome has emerged as a critical component of the tumor microenvironment (TME), playing a significant role in tumorigenesis, pathological classification, metastasis, and prognosis. The nutrient‐rich, hypoxic, acidic, and immunosuppressive nature of the TME facilitates the establishment of diverse intratumoral microbiome communities. In turn, the intratumoral microbiome further contributes to the formation of cold TME through mechanisms such as genetic and epigenetic alterations, pro‐inflammatory responses, immune modulation, tumor metastasis, and enhanced drug resistance. Targeting and eliminating the intratumoral microbiome using nanotechnology presents a unique therapeutic strategy for overcoming chemotherapy resistance and improving the immunosuppressive TME. This review summarizes the microbial characteristics of various tumors and microbiome‐mediated oncogenic mechanisms, with particular emphasis on recent advancements in nanotechnology aimed at eliminating the intratumoral microbiome and reprogramming the cold TME, thereby enhancing the efficacy of tumor immunotherapy. Our aim is to provide valuable insights to strengthen the effectiveness of tumor immunotherapy.