ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1497279
This article is part of the Research TopicBiomarker-Guided Strategies in NSCLC ImmunotherapyView all 7 articles
Investigating subregional PD-L1 expression within primary tumor to predict clinical outcome in advanced NSCLC patients who received ICB-based therapy
Provisionally accepted
- The First Affiliated Hospital of Soochow University, Suzhou, China
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Background: Programmed cell death-ligand 1 (PD-L1) immunohistochemical expression currently is the only approved useful biomarker associated with the PD-1/PD-L1 immune checkpoint blockade (ICB) efficacy for Non-Small Cell Lung Carcinoma (NSCLC) patients. However, different tumor biopsy strategies could reflect the substantial heterogeneity of PD-L1 within the same tumor (spatial heterogeneity). Therefore, we aimed to explore the impact of spatial heterogeneity on the predictive value of PD-L1 expression in NSCLC patients on the ICB treatment after two cycles. Methods: All consecutive subjects with NSCLC receiving first-line ICB-based therapy for at least two cycles between January 2020 and March 2024 were enrolled and classified according to the biopsy strategies. Transbronchial lung biopsy (TBLB) or transbronchial mucosal biopsy was performed to obtain samples from primary tumor superficial (PTsup) region. And endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) or percutaneous cutting needle biopsy (PCNB) was to get primary tumor deep region (PTdeep). The predictive capacity of PD-L1 TPS to ORR from these two sites was assessed and compared by logistic regression analysis and ROC curve analysis. It was also expanded the prognostic value of PTdeep-and PTsup-related PD-L1 TPS to PFS by performing Propensity score matching as well as stratified analysis. Results: Among NSCLC receiving ICB therapy, PTsup-related PD-L1 TPS ≥ 50% was not associated with higher ORR (15.8% vs. 26.1%, P=0.197) by stratified analysis. Instead, PTdeep-related PD-L1 TPS ≥ 50% could bring substantially higher ORR than those with TPS < 50% (52.4% vs. 17.4%, P=0.025). Further, cross analysis displayed that the PD-L1 TPS <50% from superficial or deep subregion reached relatively similar ORR (15.8% vs. 17.4%, P=0.861), whereas patients with PTdeep-related PD-L1 TPS ≥50% manifested higher ORR than those with TPS ≥50% (52.4% vs. 26.1%, P=0.036). Moreover, PTdeep-related PD-L1 yielded best performance in Area Under Curve (AUC) to predict
Keywords: PD-L1, Immunotherapy, heterogeneity, predictive biomarker, tumor response
Received: 16 Sep 2024; Accepted: 03 Oct 2025.
Copyright: © 2025 Zhou, Zhu, Mao, Su and CHEN. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: CHENG CHEN, chencheng@suda.edu.cn
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