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

Author

Listed:
  • Dominic Schmid

    (University of Basel and University Hospital of Basel
    University Hospital of Basel)

  • Bettina Sobottka

    (University of Zurich)

  • Massimiliano Manzo

    (University of Basel)

  • Marta Trüb

    (University of Basel and University Hospital of Basel
    University Hospital of Basel)

  • Katharina Leonards

    (University of Basel)

  • Petra Herzig

    (University of Basel and University Hospital of Basel
    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
    University Hospital of Basel)

  • Miklos Pless

    (Swiss Cancer Institute
    Cantonal Hospital Winterthur)

  • Adrienne Bettini

    (HFR Fribourg)

  • Martin Früh

    (Cantonal Hospital St. Gallen
    Inselspital University Hospital Berne)

  • Laetitia A. Mauti

    (Cantonal Hospital Winterthur)

  • Christian Britschgi

    (Cantonal Hospital Winterthur
    University Hospital Zurich)

  • Solange Peters

    (University Hospital Lausanne CHUV)

  • Michael Mark

    (Cantonal Hospital Graubünden
    Università della Svizzera Italiana)

  • 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
    University Hospital of Basel
    Cantonal Hospital Baden)

  • Viktor Hendrik Koelzer

    (University of Zurich
    University of Basel)

  • Alfred Zippelius

    (University of Basel and University Hospital of Basel
    University Hospital of Basel)

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.

Suggested Citation

  • Dominic Schmid & Bettina Sobottka & Massimiliano Manzo & Marta Trüb & Katharina Leonards & Petra Herzig & Oluwaseun Rume-Abiola Oyewole & Philip Jermann & Stefanie Hayoz & Spasenija Savic Prince & Giu, 2025. "Tumor immune dynamics and long-term clinical outcome of stage IIIA NSCLC patients treated with neoadjuvant chemoimmunotherapy," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63696-5
    DOI: 10.1038/s41467-025-63696-5
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