The Crosstalk between Microbiome and Immunotherapeutics: Myth or Reality

SIMPLE SUMMARY: The gut microbiota can mediate the balance between human health and disease, making the microbiome a critical organ. The gut microbiota can locally and systemically regulate the host’s immune system. Cancer immunotherapy has evolved as an essential method for treating cancer patients. Rapidly evolving data suggest that the microbiota influences the therapeutic efficacy of immunotherapy, such as immune checkpoint inhibitors. However, the specific effect of the gut microbiota on immunotherapy-treated malignancies remains unclear, and multiple reports have been released with conflicting results. The association between the gut microbiota with cancer immunology and immunotherapy is discussed here, with an emphasis on the relationship with immunotherapy outcomes. ABSTRACT: The gut microbiome refers to microorganisms and their genetic material influencing local and systemic inflammation. Inflammation is known to contribute to cancer development, progression, and treatment. Evidence suggests that modulating the gut microbiome may affect responses to various cancer therapies. The gut microbiota has been suggested to have an impact on immunotherapy efficacy, especially the currently widely used immune checkpoint inhibitors in various malignancies. Microbial interventions like fecal microbiota transplantation, various probiotics, or even antibiotics can increase or decrease the tumor’s sensitivity to immunotherapy. However, not all tumors react in the same manner, highlighting the tumor microenvironment heterogeneity across tumor types and the influence this has on the crosstalk between the microbiome and therapy outcomes. In this study, we intend to review the association between the gut microbiota and immunotherapy response in cancer patients and the factors regulating this interaction.