Tumor immune dynamics and long-term clinical outcome of stage IIIA NSCLC patients treated with neoadjuvant chemoimmunotherapy.
Year: 2025
Type: article
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. 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.
DOI: 10.48620/91618
Authors: Schmid, Dominic, Sobottka, Bettina, Manzo, Massimiliano, Trüb, Marta, Leonards, Katharina, Herzig, Petra, Oyewole, Oluwaseun Rume-Abiola, Jermann, Philip, Hayoz, Stefanie, Savic Prince, Spasenija, Tochtermann, Giulia, Natoli, Marina, Pless, Miklos, Bettini, Adrienne, Früh, Martin, Mauti, Laetitia A, Britschgi, Christian, Peters, Solange, Mark, Michael, Ochsenbein, Adrian F., Janthur, Wolf-Dieter, Waibel, Christine, Mach, Nicolas, Froesch, Patrizia, Buess, Martin, Bohanes, Pierre, Gonzalez, Michel, Alborelli, Ilaria, Rothschild, Sacha I, Koelzer, Viktor Hendrik, Zippelius, Alfred
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7084604368
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