Longitudinal Analysis of Peripheral Blood CD4+ T-Cell Profiles and Clinical Outcomes in Metastatic Non-Small-Cell...

Bronchoscopic cryotherapy is routinely used for endobronchial tumor debulking, but may also exert systemic immunologic effects that could interact with immune checkpoint blockade. We investigated peripheral blood T-cell dynamics following bronchoscopic cryotherapy and subsequent pembrolizumab-based first-line therapy in metastatic non-small-cell lung cancer (NSCLC). In this prospective, randomized, controlled single-center study, patients with metastatic NSCLC were randomized into treatment groups of bronchoscopic cryotherapy performed 7 (±1) days before standard-of-care pembrolizumab (with or without platinum-based chemotherapy) or to standard-of-care therapy alone. Peripheral blood mononuclear cells were analyzed by flow cytometry at baseline, week 3, and week 6. Radiologic response was assessed using RECIST 1.1. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier test and Cox regression. Flow cytometry was performed on 34 cryotherapy and 42 control patients. The cryotherapy group demonstrated a decrease in circulating CD4+ T cells (p = 0.002) and an increase in circulating CD8+ T cells (p = 0.013) by week 6. CD25+FOXP3+CD4+ Tregs decreased from baseline to week 3 (p = 0.024) and remained reduced through week 6. Overall response rate was higher in the cryotherapy group (41.2% vs. 16.7%; p = 0.022), while PFS and OS were numerically longer, although not statistically different (median PFS 9.5 vs. 5.3 months; median OS 17.6 vs. 14.8 months). The decrease in Tregs at week 3 was observed to predict better PFS. In patients with metastatic NSCLC receiving first-line pembrolizumab with or without chemotherapy, the addition of bronchoscopic cryotherapy was associated with a detectable peripheral immune remodeling and a higher objective response rate, whereas PFS and OS were numerically longer but not statistically different.