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

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Title: Tumor immune dynamics and long-term clinical outcome of stage IIIA NSCLC patients treated with neoadjuvant chemoimmunotherapy.
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.
Source: Nature Communications; 9/30/2025, Vol. 16 Issue 1, p1-15, 15p
Subject Terms: NON-small-cell lung carcinoma, NEOADJUVANT chemotherapy, TREATMENT effectiveness, BIOMARKERS, TUMOR microenvironment, T cell receptors, PROGRESSION-free survival, T-cell exhaustion
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. Neoadjuvant immunochemotherapy against NSCLC has been tested in clinical trials. Here, the authors follow up longer-term survival and measure immune cell phenotype changes in a single-arm phase II clinical trial of neoadjuvant immunochemotherapy, indicating association of intratumoural TCR diversity and CD8 T cell positioning. [ABSTRACT FROM AUTHOR]
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Database: Complementary Index
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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<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. Neoadjuvant immunochemotherapy against NSCLC has been tested in clinical trials. Here, the authors follow up longer-term survival and measure immune cell phenotype changes in a single-arm phase II clinical trial of neoadjuvant immunochemotherapy, indicating association of intratumoural TCR diversity and CD8 T cell positioning. [ABSTRACT FROM AUTHOR]
ISSN:20411723
DOI:10.1038/s41467-025-63696-5