Towards modulating the gut microbiota to enhance the efficacy of immune-checkpoint inhibitors.

The gut microbiota modulates immune processes both locally and systemically. This includes whether and how the immune system reacts to emerging tumours, whether antitumour immune responses are reactivated during treatment with immune-checkpoint inhibitors (ICIs), and whether unintended destructive immune pathologies accompany such treatment. Advances over the past decade have established that the gut microbiota is a promising target and that modulation of the microbiota might overcome resistance to ICIs and/or improve the safety of treatment. However, the specific mechanisms through which the microbiota modulates antitumour immunity remain unclear. Understanding the biology underpinning microbial associations with clinical outcomes in patients receiving ICIs, as well as the landscape of a 'healthy' microbiota would provide a critical foundation to facilitate opportunities to effectively manipulate the microbiota and thus improve patient outcomes. In this Review, we explore the role of diet and the gut microbiota in shaping immune responses during treatment with ICIs and highlight the key challenges in attempting to leverage the gut microbiome as a practical tool for the clinical management of patients with cancer.

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