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. 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<sup>+</sup> 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<sup>+</sup> PD-1<sup>+</sup> CD8<sup>+</sup> T cells and elevated levels of CCL15 post-treatment are seen in patients with sustained therapeutic benefit. NCT02572843.
Authors
- Katharina Leonards (ORCID: https://orcid.org/0000-0002-4004-3473)
- Viktor Hendrik Koelzer (ORCID: https://orcid.org/0000-0001-9206-4885)
- Marina Natoli (ORCID: https://orcid.org/0000-0002-0270-0225)
- Sacha I. Rothschild (ORCID: https://orcid.org/0000-0003-1304-9340)
- Spasenija Savic Prince (ORCID: https://orcid.org/0000-0002-4065-5111)
- Nicolas Mach (ORCID: https://orcid.org/0000-0001-8944-1088)
- Olufemi Oyeleye Oyewole (ORCID: https://orcid.org/0000-0003-2432-247X)
- Massimiliano Manzo
- Petra Herzig (ORCID: https://orcid.org/0000-0001-7745-5335)
- Christine Waibel
- Bettina Sobottka (ORCID: https://orcid.org/0000-0002-0890-5248)
- Adrian F. Ochsenbein (ORCID: https://orcid.org/0000-0003-1773-5436)
- Michel González (ORCID: https://orcid.org/0000-0001-8705-4279)
- Stefanie Hayoz (ORCID: https://orcid.org/0000-0002-2265-6559)
- Ilaria Alborelli (ORCID: https://orcid.org/0000-0001-7849-3958)
- Dominic Schmid (ORCID: https://orcid.org/0000-0003-4821-6495)
- Solange Peters (ORCID: https://orcid.org/0000-0002-0412-7143)
- Michael Mark
- Alfred Zippelius (ORCID: https://orcid.org/0000-0003-1933-8178)
- Martin Buess (ORCID: https://orcid.org/0000-0001-6590-1203)
- Philip M. Jermann (ORCID: https://orcid.org/0000-0002-8836-4946)
- Christian Britschgi (ORCID: https://orcid.org/0000-0001-8831-1564)
- Giulia Tochtermann (ORCID: https://orcid.org/0000-0001-5157-431X)
- Patrizia Froesch (ORCID: https://orcid.org/0000-0002-8140-1249)
- Laetitia Mauti (ORCID: https://orcid.org/0000-0002-6652-1947)
- Pierre Bohanes
- Marta Trüb
- Adrienne Bettini
- Miklos Pless
- Martin Früh
- Wolf-Dieter Janthur (ORCID: https://orcid.org/0009-0005-4139-2260)
Institutions
- University of Basel (CH)
- University of Zurich (CH)
- University of St.Gallen (CH)
- University Hospital of Bern (CH)
- Centre Hospitalier Universitaire Vaudois (CH)
- University Hospital of Basel (CH)
- Kantonsspital Winterthur (CH)
- University Hospital of Zurich (CH)
- Institute of Oncology Research (CH)
- Swiss Cancer League (CH)
- University Hospital of Geneva (CH)
- Kantonsspital Baden (CH)
- Department of Biomedicine Basel (CH)
- St. Claraspital (CH)
- Swiss Group For Clinical Cancer Research (CH)
- Kantonsspital Graubünden (CH)
- Kantonsspital Aarau (CH)
- Università della Svizzera italiana (CH)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-30
- DOI
- https://doi.org/10.1038/s41467-025-63696-5
- Citations
- 2
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 2.09
Funders
- Gateway for Cancer Research
- AstraZeneca
- Rising Tide Foundation for Clinical Cancer Research
- Rising Tide Foundation