Multi-omics of the gut microbial ecosystem in patients with microsatellite-instability-high gastrointestinal cancer resistant to immunotherapy.

ABSTRACT: Despite the encouraging efficacy of anti-PD-1/PD-L1 immunotherapy in microsatellite-instability-high/deficient mismatch repair (MSI-H/dMMR) advanced gastrointestinal cancer, many patients exhibit primary or acquired resistance. Using multi-omics approaches, we interrogate gut microbiome, blood metabolome, and cytokines/chemokines of patients with MSI-H/dMMR gastrointestinal cancer (N = 77) at baseline and during the treatment. We identify a number of microbes (e.g., Porphyromonadaceae) and metabolites (e.g., arginine) highly associated with primary resistance to immunotherapy. An independent validation cohort (N = 39) and mouse model are used to further confirm our findings. A predictive machine learning model for primary resistance is also built and achieves an accuracy of 0.79 on the ext

SUBMITTER: Cheng S 

PROVIDER: S-EPMC10829783 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature