Gut microbiome metabolites, molecular mimicry, and species-level variation drive long-term efficacy and adverse event outcomes in lung cancer survivors.

ABSTRACT:

Background

The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms.

Methods

We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts).

Findings

The ICI benefit group was enriched for propionate (P = 0.01) and butyrate/isobutyrate (P = 0.12) compared with the resistance group, which was validated in the McC

SUBMITTER: Liu X 

PROVIDER: S-EPMC11550776 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature