The gut microbiota improves the efficacy of immune-checkpoint inhibitor immunotherapy against tumors: From association to cause and effect

Abstract

Immune-checkpoint inhibitors (ICIs), including anti-PD-1/PD-L1 therapeutic antibodies, have markedly enhanced survival across numerous cancer types. However, the limited number of patients with durable benefits creates an urgent need to identify response biomarkers and to develop novel strategies so as to improve response. It is widely recognized that the gut microbiome is a key mediator in shaping immunity. Additionally, the gut microbiome shows significant potential in predicting the response to and enhancing the efficacy of ICI immunotherapy against cancer. Recent studies encompassing mechanistic analyses and clinical trials of microbiome-based therapy have shown a cause-and-effect relationship between the gut microbiome and the modulation of the ICI immunotherapeutic response, greatly contributing to the establishment of novel strategies that will improve response and overcome resistance to ICI treatment. In this review, we outline the current state of research advances and discuss the future directions of utilizing the gut microbiome to enhance the efficacy of ICI immunotherapy against tumors.

Keywords: Gut microbiome; Immune-checkpoint inhibitor; Mechanisms; Microbiome-based therapy; PD-1/PD-L1.