Microbiome landscape and association with response to immune checkpoint inhibitors in advanced solid tumors: SCRUM-Japan MONSTAR-SCREEN

Abstract Although the gut microbiome is associated with cancer development and progression, little is known about the effects of the gut microbiome landscape and the efficacy of immune checkpoint inhibitors (ICIs) across cancers. We investigated the association between the microbiome, clinical features, and ICIs efficacy across cancer types in a large nationwide screening project for solid tumors (SCRUM-Japan MONSTAR-SCREEN). In the chemotherapy-naïve cohort (n=817), there was a high proportion of oral bacteria in the feces of patients who used proton pump inhibitors (PPIs) or had upper gastrointestinal cancers, especially in those with gastric cancer who underwent gastrectomy. Among patients treated with ICIs (n=333), alpha diversity, such as the number of amplicon sequence variants in feces, was not a predictive marker of ICI treatment across cancers. Still, using PPIs and high levels of oral bacteria in feces attenuated ICIs efficacy. This study provides insights into the strategies for improving ICIs efficacy.