2025/09/30 by Schmid, Dominic, Sobottka, Bettina, Manzo, Massimiliano +28
Medicine · Immunology and Microbiology · #Cancer Immunotherapy and Biomarkers #Lung Cancer Diagnosis and Treatment #Immunotherapy and Immune Responses
paper · doi:10.5167/uzh-280927
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. We report secondary outcomes of median event-free survival (EFS) of 4.0 years and median overall survival not being reached after a median follow-up of 5.4 years. Computer-aided spatial image analysis emphasizes the importance of CD8 T cell positioning in tumors, and larger tertiary lymphoid structures in pre-treatment biopsies correlate with improved EFS. Genomic techniques reveal the association of intratumoral TCR diversity with response. Finally, circulating proliferating CD39 PD-1 CD8 T cells and elevated levels of CCL15 post-treatment are seen in patients with sustained therapeutic benefit. NCT02572843.