Exploring the emerging role of the microbiome in cancer immunotherapy

The activity of the commensal microbiota significantly impacts human health and has been linked to the development of many diseases, including cancer. Gnotobiotic animal models have shown that the microbiota has many effects on host physiology, including on the development and regulation of immune responses. More recently, evidence has indicated that the microbiota can more specifically influence the outcome of cancer immunotherapy. Therapeutic interventions to optimize microbiota composition to improve immunotherapy outcomes have shown promise in mouse studies. Ongoing endeavors are translating these pre-clinical findings to early stage clinical testing. In this review we summarize 1) basic methodologies and considerations for studies of host-microbiota interactions; 2) experimental evidence towards a causal link between gut microbiota composition and immunotherapeutic efficacy; 3) possible mechanisms governing the microbiota-mediated impact on immunotherapy efficacy. Moving forward, there is need for a deeper understanding of the underlying biological mechanisms that link specific bacterial strains to host immunity. Integrating microbiome effects with other tumor and host factors regulating immunotherapy responsiveness versus resistance could facilitate optimization of therapeutic outcomes.