Tumor immune dynamics and long-term clinical outcome of stage IIIA NSCLC patients treated with neoadjuvant chemoimmunotherapy

Neoadjuvant chemoimmunotherapy offers promise to improve outcomes for patients with resectable non-small cell lung cancer (NSCLC). Yet, not all patients derive treatment benefits and reliable biomarkers of response are still lacking. We here assess the long-term clinical outcome of neoadjuvant chemotherapy and perioperative anti-PD-L1 inhibition in resectable stage IIIA NSCLC in the SAKK 16/14 trial and provide a comprehensive characterization of anti-tumor immune responses for biomarker-based treatment personalization. At a median follow-up of 5.3 years, the median event-free survival (EFS) was 4.0 years while median overall survival was not reached. Computer-aided spatial image analysis emphasized the importance of CD8+ T cell positioning in tumors, and larger tertiary lymphoid structures in pre-treatment biopsies correlated with improved EFS. Genomic techniques revealed the association of intratumoral TCR diversity with response. Finally, circulating proliferating CD39 ⁺ PD-1 ⁺ CD8 ⁺ T cells and elevated levels of CCL15 post-treatment were seen in patients with sustained therapeutic benefit.