Respiratory microbiota diversity as a predictive biomarker for the efficacy of PD‑1 blockades in patients with advanced non‑small cell lung cancer: A retrospective exploratory study

Despite advancements in immunotherapy, particularly regarding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 blockades, the clinical outcomes in non-small cell lung cancer (NSCLC) remain variable with limited predictive biomarkers currently available. The present study investigated respiratory microbiota diversity as a potential biomarker to predict the efficacy of PD-1 blockades in patients with advanced NSCLC. A retrospective analysis was conducted on 60 patients treated with PD-1 blockades from May 2019 to May 2023. Clinical data were collected and respiratory microbiota from deep induced sputum specimens were analyzed using 16S rRNA gene sequencing. An index of respiratory microbiota α diversity was applied and exploratory analysis was performed accordingly. The objective response rate (ORR) and disease control rate among the 60 patients receiving PD-1 blockades was 23.3% (95% CI, 13.4-36.0%) and 58.3% (95% CI, 44.9-70.9%), respectively. Analysis of prognostic data of patients with advanced NSCLC receiving PD-1 blockades monotherapy demonstrated a median progression-free survival of 3.4 months (95% CI, 2.54-4.26) and a median overall survival (OS) of 12.3 months (95% CI, 6.29-18.31). Patients were stratified into high and low α diversity groups based on the Shannon diversity index of respiratory microbiota. The ORR was increased in the high diversity group (26.7%) compared with that of the low diversity group (20.0%), although the difference was not statistically significant (P=0.542). Notably, the high diversity group demonstrated a longer median PFS (3.9 vs. 2.8 months; P=0.017) and median OS (16.8 vs. 6.8 months; P=0.016) compared with that of the low diversity group. These findings suggested that PD-1 blockades demonstrate promising therapeutic activity for patients with previously treated advanced NSCLC in clinical practice. Respiratory microbiota α diversity might serve as a potential biomarker to predict the efficacy of PD-1 blockades monotherapy in patients with advanced NSCLC in the future. Therefore, further prospective studies are warranted to validate these findings and to explore the underlying mechanisms by which respiratory microbiota might modulate the immune response to cancer therapy.