Friends close, enemies closer: the complex role of the microbiome in antitumor immunity

Immunotherapy has achieved remarkable advances in cancer treatment by harnessing the immune system to combat tumors, yet its effectiveness remains inconsistent across patients and tumor types. The microbiota, a diverse assemblage of microorganisms residing at host barrier surfaces, is pivotal in shaping immune responses. This review explores the direct and indirect mechanisms via which the microbiota modulates antitumor immune responses both locally within the tumor microenvironment and systemically by affecting distant tumors. We discuss recent findings linking microbiota-derived metabolites and microbiota-derived antigens with antitumor immunity and immunotherapy response. Additionally, we discuss recent advances in microbiome-based therapies, including fecal microbiota transplantation. We propose the use and development of new analytical techniques to further characterize the complex functions and interactions between the microbiome and immune system. To conclude, we outline recommendations for future research and therapeutic approaches to leverage the microbiome to improve current immunotherapies.