Cancer immunotherapies harness the power of the immune system to target cancer cells that express tumor-associated antigens. Immune checkpoint inhibitors, such as monoclonal antibodies against inhibitory T cell receptors, i.e., PD-1/PD-L1 and CTLA-4, allow cancer cells that have evaded the immune system to be recognized as non-self by activated T lymphocytes. These therapeutic strategies have had clinical success; however, cancer immunotherapies fail in many patients, and the reasons for these mixed responses are not well understood. Thus, there is significant interest in identifying factors that modulate immune responses and influence the efficacy of immunotherapies. Evolving evidence has shown that one such factor is the constellation of commensal microbes inhabiting the human body, the microbiota.

The human microbiota is comprised of a vastly diverse array of archaea, bacteria, viruses, fungi, and unicellular protozoa that play critical roles in maintaining physiological homeostasis, including influencing the development and function of the peripheral immune system and anti-tumor immunosurveillance. Perturbations in the composition and balance of the microbiota (i.e., dysbiosis) can significantly modulate the immune system and result in pathologic conditions, such as chronic inflammation and cancer. It has emerged that the presence or absence of distinct commensal microbes can have a marked effect on the initiation and progression of cancers as well as host responses to cancer immunotherapies.

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