Microbial Influence on Immune Checkpoint Inhibitor Therapy in Non-Small Cell Carcinoma: The Gut-Lung-Immune Axis

Area of Science:

• Oncology
• Immunology
• Microbiome Research

Background:

• Non-small cell lung cancer (NSCLC) is a leading cause of cancer death globally.
• Immune checkpoint inhibitors (ICIs) have improved NSCLC treatment but face resistance and immune-related adverse events (irAEs).
• The gut microbiome is increasingly recognized as a factor influencing NSCLC patient outcomes, particularly with ICI therapy.

Purpose of the Study:

• To review the role of gut, tumor, and circulating microbiota in NSCLC immunotherapy.
• To synthesize current clinical and mechanistic data on the gut-lung-immune axis in NSCLC.
• To explore microbiome-based biomarkers for predicting ICI response and toxicity.

Main Methods:

• Review of current clinical and mechanistic studies on microbiota and NSCLC immunotherapy.
• Analysis of microbial signatures associated with ICI efficacy and irAEs.
• Evaluation of emerging microbial biomarkers for treatment prediction.

Main Results:

• Specific gut and tumor microbial compositions, including *Akkermansia muciniphila* and *Bifidobacterium*, correlate with better ICI response.
• Microbial dysbiosis is linked to immune suppression, resistance to ICIs, and increased irAEs.
• Microbiome-based biomarkers (fecal profiles, cfDNA, TOPOSCORE) show potential for predicting treatment outcomes.

Conclusions:

• The gut-lung-immune axis is a critical regulator of ICI efficacy and toxicity in NSCLC.
• Microbiome-informed strategies offer potential for personalized and safer NSCLC immunotherapy.
• Targeting the microbiome may enhance treatment effectiveness and reduce adverse events in NSCLC patients.