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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Tuesday, October 21, 2025
The results of an analysis of the multicenter, single-arm phase II SAKK 16/14 trial, which were published in Nature Communications, highlighted the potential of a comprehensive approach combining digital pathology with multiplexed analytical technologies to delineate and enhance the understanding of tumor immune cell dynamics. According to Alfred Zippelius, MD, PhD, of University of Basel and University Hospital of Basel, Switzerland, and colleagues, they may help guide more effective neoadjuvant therapies for patients with non–small cell lung cancer (NSCLC).
“Neoadjuvant chemoimmunotherapy offers promise to improve outcomes for patients with resectable NSCLC,” the investigators commented. However, they emphasized that challenges remain, noting that “not all patients derive treatment benefits, and reliable biomarkers of response are still lacking,” which provided the rationale for their work.
In the trial, patients with resectable stage IIIA NSCLC underwent neoadjuvant chemotherapy and perioperative anti–PD-L1 therapy, leading to a previously reported major pathologic response rate of 60%, pathologic complete response rate of 18%, and 12-month event-free survival rate of 73%. The present analysis assessed long-term clinical outcomes and included several laboratory investigations using pretreatment and posttreatment patient samples to provide a comprehensive characterization of antitumor immune responses for biomarker-based treatment personalization.
Secondary outcome analysis revealed a median event-free survival of 4.0 years and an unreached median overall survival after a median follow-up of 5.4 years. According to the investigators, computer-aided spatial image analysis highlighted the importance of CD8-positive T-cell positioning within tumors; larger tertiary lymphoid structures in pretreatment biopsies were found to be associated with improved event-free survival. Genomic analyses demonstrated a link between intratumoral T-cell receptor diversity and response. Patients with sustained therapeutic benefit exhibited circulating proliferating CD39-positive, PD-1–positive, CD8-positive T cells and elevated posttreatment levels of CCL15.
“Future endeavors should focus on further validating these markers in larger, controlled trials and exploring their potential to guide individualized treatment strategies,” the investigators concluded.
Disclosure: For full disclosures of the study authors, visit nature.com.
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