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

Dominic Schmid (), Bettina Sobottka, Massimiliano Manzo, Marta Trüb, Katharina Leonards, Petra Herzig, Oluwaseun Rume-Abiola Oyewole, Philip Jermann, Stefanie Hayoz, Spasenija Savic Prince, Giulia Tochtermann, Marina Natoli, Miklos Pless, Adrienne Bettini, Martin Früh, Laetitia A. Mauti, Christian Britschgi, Solange Peters, Michael 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 Hendrik Koelzer and Alfred Zippelius ()
Additional contact information
Dominic Schmid: University of Basel and University Hospital of Basel
Bettina Sobottka: University of Zurich
Massimiliano Manzo: University of Basel
Marta Trüb: University of Basel and University Hospital of Basel
Katharina Leonards: University of Basel
Petra Herzig: University of Basel and University Hospital of Basel
Oluwaseun Rume-Abiola Oyewole: University of Basel
Philip Jermann: University of Basel
Stefanie Hayoz: Swiss Cancer Institute
Spasenija Savic Prince: University of Basel
Giulia Tochtermann: University of Zurich
Marina Natoli: University of Basel and University Hospital of Basel
Miklos Pless: Swiss Cancer Institute
Adrienne Bettini: HFR Fribourg
Martin Früh: Cantonal Hospital St. Gallen
Laetitia A. Mauti: Cantonal Hospital Winterthur
Christian Britschgi: Cantonal Hospital Winterthur
Solange Peters: University Hospital Lausanne CHUV
Michael Mark: Cantonal Hospital Graubünden
Adrian F. Ochsenbein: Inselspital University Hospital Berne
Wolf-Dieter Janthur: Cantonal Hospital Aarau
Christine Waibel: Cantonal Hospital Baden
Nicolas Mach: University Hospital Geneva
Patrizia Froesch: Oncology Institute of Southern Switzerland
Martin Buess: St Claraspital
Pierre Bohanes: Centre de Chimiothérapie Anti-Cancéreuse
Michel Gonzalez: University Hospital Lausanne CHUV
Ilaria Alborelli: University of Basel
Sacha I. Rothschild: University of Basel and University Hospital of Basel
Viktor Hendrik Koelzer: University of Zurich
Alfred Zippelius: University of Basel and University Hospital of Basel

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63696-5

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