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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月30日

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  • 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,
  • Alfred Zippelius

摘要

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.