Work

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

Year: 2026

Type: article

Abstract: Lung cancer, particularly non-small cell lung cancer (NSCLC), remains the leading cause of cancer mortality worldwide. While immune checkpoint inhibitors (ICIs) have revolutionized treatment, primary and acquired resistance, and immune-related adverse events (irAEs) limit their therapeutic efficacy. Recent evidence highlights the gut and local microbial communities as a modifiable determinant of NSCLC outcomes, especially in the context of ICI use. Emerging data support the concept of a gut–lung-immune axis, a tridirectional communication pathway, in which gut and lung microbial communities influence local and systemic antitumor immunity through immune cell trafficking, cytokine signaling, and microbial-derived metabolites. In this review, we synthesize current clinical and mechanistic studies examining the role of gut, tumor-resident, and circulating microbiota in shaping ICI efficacy and toxicity in NSCLC. Distinct gut and tumor microbial signatures, such as the abundance of Akkermansia muciniphila and Bifidobacterium, correlate with improved ICI response, whereas dysbiosis promotes immune suppression, resistance, and irAEs. Additionally, we highlight emerging microbial-based biomarkers, including fecal microbial profiles, circulating microbial DNA, and composite tools such as TOPOSCORE, which show promise for predicting response, toxicity, and optimal treatment duration. Overall, these findings underscore the gut–lung-immune axis as a key regulator of immunotherapy outcomes in NSCLC and suggest that microbiome-informed strategies may enable more precise, effective, and safer personalization of ICI therapy.

Source: Cancers

DOI: 10.3390/cancers18121948

Authors: Haroon Ali, Bingqing Xie, Jun Yang, Urooba Nadeem

Institution: The University of Texas Southwestern Medical Center

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499