作者
Dominic Schmid,Anna Bettina Sobottka-Brillout,Massimiliano Manzo,Marta Trüb,Katharina Leonards,Petra Herzig,P. Jermann,Stefanie Hayoz,Marina Natoli,Spasenija Savic Prince,Giulia Tochtermann,Miklos Pless,Adrienne Bettini,Martin Früh,Laetitia Mauti,Christian Britschgi,Solange Peters,Michaela Mark,Adrian F. Ochsenbein,Wolf-Dieter Janthur,Christine Waibel,Nicolas Mach,Patrizia Froesch,Martin Buess,Pierre Bohanes,Michel Gonzalez,Ilaria Alborelli,Sacha I. Rothschild,Viktor H. Koelzer,Alfred Zippelius
摘要
Abstract 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.