Investigating subregional PD-L1 expression within primary tumors to predict clinical outcomes in advanced NSCLC patients who received ICB-based therapy.

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 the primary tumor superficial (PT Results: Among NSCLC receiving ICB therapy, PT Conclusions: PD-L1 from the deep subregion is a more solid predictive biomarker of both short- and long-time efficacies of ICB-based therapy, and optimizing the assessment of spatial heterogeneity provides a new perspective for clinicians to screen advanced NSCLC patients who can benefit from ICB-based therapy.