Microbial manipulators: Fusobacterium nucleatum modulates the tumor immune microenvironment in colorectal cancer

Fusobacterium nucleatum, a microorganism ordinarily detected in the oral cavity, is considered as a pathobiont related to periodontitis and a range of human diseases, including colorectal cancer (CRC). The dynamics of how F. nucleatum encourages CRC tumorigenesis and progression has been well-investigated. Recently, mechanisms by which F. nucleatum regulates the tumor immune microenvironment (TiME) and subsequently alters CRC oncogenesis and advancement have drawn more and more attention. The TiME consists of immune cells and non-cellular components like cytokines in the tumor microenvironment. By contacting immune cells in the TiME, F. nucleatum fosters an immunosuppressive TiME, diminishes anti-tumor immunity and promotes CRC development. This also allows F. nucleatum to interfere with immunotherapy process and efficacy. In this review, we present a summary of how F. nucleatum interacts with immune cells within the TiME, thereby promoting CRC progression and influencing CRC immunotherapy effectiveness. This review also integrates insights from molecular pathological epidemiology (MPE) to contextualize host-microbe-environment interactions in CRC. We identify gaps in current knowledge and outline possible future research paths. These findings may offer valuable insights for future mechanistic research and the development of novel therapeutic strategies.