Identification and validation of intratumoral microbiome associated with sensitization to immune checkpoint inhibitors.

Abstract

As a part of the commensal microbiome, the regulatory role of the intratumoral microbiome in tumor immunity is gradually revealed. However, the relationship between the intratumoral microbiome and the efficacy of immune checkpoint inhibitors (ICIs) clinical treatment remains unclear. Here, we collect RNA sequencing (RNA-seq) data and clinical information from publicly available ICIs therapy cohorts. By developing an improved bioinformatics pipeline to identify the intratumoral microbiome and performing a comprehensive association analysis, we find that the intratumoral microbiome is associated with response to ICIs and characteristics of the tumor microenvironment (TME). In vivo experiments demonstrate that intratumoral injection of Burkholderia cepacia, Priestia megaterium, or Corynebacterium kroppenstedtii, which were selected from our analysis results, would synergize with anti-PD-1 therapy to inhibit tumor growth and enhance antitumor immunity. Our findings highlight the essential role of the intratumoral microbiome in the clinical effectiveness differences of ICIs, suggesting its potential in future ICIs combination therapy.