Roles of microbiota in response to cancer immunotherapy

Immunotherapy, which shows great promise for treating patients with metastatic malignancies, has dramatically changed the therapeutic landscape of cancer, particularly subsequent to the discovery of immune checkpoint inhibitors. However, the responses to immunotherapy are heterogeneous and often transient. More problematic is that a high proportion of patients with cancer are resistant to such therapy. Much effort has been expended to identify reliable biomarkers that accurately predict clinical responses to immunotherapy. Unfortunately, such tools are lacking, and our knowledge of the mechanisms underlying its efficacy and safety is insufficient. The microbiota is increasingly recognized for its influence on human health and disease. Microbes create a pro- or an anti-inflammatory environment through complex interactions with host cells and cytokines. Emerging evidence indicates that microbes alter the efficacy and toxicity of immunotherapy by modulating the host's local and systemic immune responses. It is therefore critically important to exploit the microbiota to develop biomarkers as well as to identify therapeutic targets that can be applied to cancer immunotherapy. This review provides insights into the challenges that must be addressed to achieve these goals.