Association Between anti-PD-1/PD-L1 Immune Checkpoint Inhibitors and Type 2 Airway Inflammation in Patients with Lung Cancer: the IMMUNEO Retrospective Case Series.

BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have revolutionized lung cancer therapy, but immune-mediated complications are a growing concern, and their impact on type 2 inflammation and chronic airway disease remains unclear. Corticosteroids, standard for eosinophilic airway diseases, are detrimental in anti-PD-1/PD-L1-treated patients. OBJECTIVE: We investigated the effect of ICIs on blood eosinophil counts (BEC), chronic airway disease development and exacerbations in a real-world cohort. METHODS: This retrospective study analyzed clinical, biological, and imaging data from 127 consecutive patients treated with PD-1/PD-L1 inhibitors for non-small cell lung cancer. BEC, lung function, comorbid asthma or COPD, frequency of exacerbations, corticosteroid use werecollected. ROC curves identified eosinophil thresholds predictive of exacerbation risk. RESULTS: Half of the patients had COPD (n=47) or asthma (n=13), one third newly diagnosed, and 11 (8.7%) exacerbated on treatment, 9 of them frequently (≥2/year). BEC increased significantly during ICI, more so among exacerbators (p=0.0013). Pre-treatment BEC >275 cells/mm3 was associated with exacerbation onset, while on-treatment values >345 cells/mm3 offered better prediction (AUC 0.73, 67% sensitivity; 83% specificity). In multivariable analysis, exacerbations were negatively associated with 10% increase in FEV1 (OR=0.70; 95%CI=0.46-0.99) and positively associated with concomitant systemic corticosteroid use (OR=10.34; 95%CI=1.81-69.27), and on-treatment eosinophil rise (OR=1.15; 95%CI=1.01-1.36 per 102 cells/mm3). CONCLUSION: ICIs may unmask or amplify underlying T2 airway inflammation. A raised eosinophil count is a specific but weakly predictive signal that should prompt surveillance rather than be over-interpreted, whereas a low count is reassuring.