Abstract

Immune checkpoint inhibitors (ICIs) therapy is a novel strategy for cancer treatments in recent years. However, it was observed that most patients treated with ICIs could not get benefit from the therapy, which led to the limitation of clinical application. Motivated by potent and durable efficacy of ICIs, oncologists endeavor to explore the mechanisms of resistance to ICIs and increase the drug sensitivity. It is known that heterogeneity of gut microbiome in populations may result in different outcomes of therapy. In xenograft model, bacteria in gut have been proved as a crucial factor regulating immunotherapy efficacy. And the similar phenomenon was obtained in patients. In this review, we summarized relevant advancements about gut microbiome and ICIs. Furthermore, we focused on modulatory function of gut microbiome in ICIs therapy and possible antitumor mechanism of specific commensals in ICIs treatment. We propose that gut microbiome is an important predictive factor, and manipulation of gut microbiome is feasible to elevate response rate in ICIs therapy.

Highlights

  • Various bacteria populating in mammal gastrointestinal tract are an indispensable part in intestine ecosystem and play a pivotal role in gut barrier [1]

  • Some bacteria in the context of Immune checkpoint inhibitors (ICIs) play a role by enhancing tumor-specific immunity, blocking inhibitory signal pathways, and promoting antigen presentation, which could be understood as downregulated cancer-immune checkpoint

  • Cancer immunotherapy includes the use of antibodies, lymphocytes, and cytokines [101, 102]

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Summary

Introduction

Various bacteria populating in mammal gastrointestinal tract are an indispensable part in intestine ecosystem and play a pivotal role in gut barrier [1]. Studies on the role of gut microbiome in ICIs efficacy Distinguished from cytotoxic therapies, ICIs mediates tumor regression via enhanced host immune activation. Trial in mouse model verified the conclusion: broad-spectrum antibiotics-treated or germ-free mice receiving fecal microbiome transplantation from non-responding individuals showed significant compromised antitumor effect of PD-1 blockade or PD-1 combined with CTLA-4 blockade [12].

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