Salivary microbial signature highlighting actinomyces as a predictor of immune-checkpoint inhibitor monotherapy response in advanced non–small cell lung cancer

作者：Silvia Cavaliere, Marta Fogolari, Michele Iuliani, Simone Foderaro, Alessio Cortellini, Sonia Simonetti, Emanuele Claudio Mingo, S. Calagna, M. Russano, B. Vincenzi, Giuseppe Tonini, Silvia Angeletti, F. Pantano · 发表于：Journal of Translational Medicine · 年份：2026 · DOI：10.1186/s12967-025-07570-4 · 被引用次数：1 · 研究领域：Cancer Immunotherapy and Biomarkers、Gut microbiota and health、Ferroptosis and cancer prognosis

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved survival in advanced non-small cell lung cancer (NSCLC), yet reliable biomarkers beyond programmed death-ligand 1 (PD-L1) expression remain limited. Increasing evidence links the gut microbiome to ICI activity, but the predictive value of the salivary microbiome is poorly defined. METHODS: We prospectively analyzed baseline saliva from 71 stage IV NSCLC patients treated with anti-PD-1/PD-L1 (ICI) monotherapy. After quality control, 70 samples underwent 16 S rRNA gene sequencing of the V1-V3 region. Microbial diversity, differential abundance (LEfSe, Mann-Whitney/Kruskal-Wallis with false discovery rate correction) and survival associations (Kaplan-Meier; Cox proportional-hazards with LASSO-based variable selection and 1000-fold bootstrap validation) were examined. In this cohort, an exploratory genus-level cut-off was derived by receiver operating characteristic (ROC) analysis. RESULTS: α-diversity and β-diversity did not differ between responders (progression-free survival (PFS) ≥ 12 months; n = 18) and non-responders (n = 52). Differential‑abundance profiling revealed a graded enrichment of the phylum Actinobacteria across all lower ranks, class Actinobacteria, order Actinomycetales, family Actinomycetaceae and genus Actinomyces,in non‑responders (LEfSe LDA > 3.5; p = 0.001 for each level; FDR ≤ 0.049). ROC analysis suggested an Actinomyces relative abundance of 11% (AUC = 0.768; sensitivity 0.94; specificity 0.4...