Microbiome Landscape and Association with Response to Immune Checkpoint Inhibitors in Advanced Solid Tumors: A...

Area of Science:

• Oncology
• Microbiome Research
• Immunotherapy

Background:

• The gut microbiome's role in cancer development and immune checkpoint inhibitor (ICI) efficacy is increasingly recognized.
• However, comprehensive data on microbiome landscape variations and their impact on ICI efficacy across diverse cancer types remain limited.

Purpose of the Study:

• To investigate the association between the gut microbiome composition, clinical features, and ICI efficacy in a large cohort of patients with advanced solid tumors.
• To determine if gut microbiome diversity or specific bacterial abundances predict ICI treatment outcomes.

Main Methods:

• Analysis of gut microbiome data from 2,180 patients with advanced solid tumors enrolled in the SCRUM-Japan MONSTAR-SCREEN project.
• Correlation of microbiome profiles with clinical features and ICI efficacy, including progression-free survival (PFS).
• Subgroup analysis focusing on patients using proton pump inhibitors (PPIs).

Main Results:

• A high prevalence of oral bacteria was observed in patients using PPIs and those with upper gastrointestinal cancers.
• Overall gut microbiome diversity did not significantly predict ICI efficacy across cancer types (HR=0.94).
• Increased oral bacteria in feces was associated with shorter PFS (median 4.34 vs. 6.97 months) and diminished ICI efficacy, especially in PPI users (median PFS 3.15 vs. 2.04 months).

Conclusions:

• Gut microbiome composition, specifically the abundance of oral bacteria, significantly impacts ICI efficacy.
• The presence of oral bacteria in the gut may reduce treatment effectiveness, particularly in patients using PPIs.
• These findings underscore the clinical relevance of microbiome profiling for optimizing cancer immunotherapy.