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. 2025 Dec 9:S2212-4403(25)01350-1.
doi: 10.1016/j.oooo.2025.11.018. Online ahead of print.

PD-L1 expression combined with immune phenotype is a potential predictor of outcome with PD-1 inhibitor monotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma

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PD-L1 expression combined with immune phenotype is a potential predictor of outcome with PD-1 inhibitor monotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma

Dong Hyun Kim et al. Oral Surg Oral Med Oral Pathol Oral Radiol. .

Abstract

Objective: Programmed cell death-ligand 1 (PD-L1) expression and immune phenotype (IP) are potential predictive biomarkers for immune checkpoint inhibitors (ICIs) in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). This study evaluated the predictive value of combining PD-L1 expression and IP in R/M HNSCC.

Study design: Forty-one R/M HNSCC patients treated with ICI were included. PD-L1 expression was evaluated using the standardized 22C3 pharmDx assay. IPs were assessed using Lunit SCOPE IO, an artificial intelligence-powered tumor-infiltrating lymphocyte analyzer.

Results: Thirty-nine patients (95.1%) were classified as PD-L1 positive (combined positive score ≥1). Overall, 27 (65.9%) had desert IP. PD-L1 expression and IP were combined to classify patients into 3 groups: group A, negative PD-L1; group B, positive PD-L1 with desert IP; group C, positive PD-L1 with non-desert IP. The median progression-free survival (PFS) was 1.2 months in group A, 2.1 months in group B, and 12.1 months in group C (P = .015). In multivariate Cox analysis, PD-L1 expression combined with IP was an independent factor for PFS, with a hazard ratio of 0.14 (P = .018) in group C and 0.37 (P = .186) in group B, relative to group A.

Conclusions: In R/M HNSCC, integrating IP with PD-L1 expression may enhance prediction of ICI outcomes.

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Conflict of interest statement

DECLARATIONS OF INTEREST BK received research funding from MSD, AstraZeneca, Bayer, and Ono Pharmaceutical Co., Ltd., and has served as an advisor for Handok, Yuhan, Trialinformatics, and ImmuneOncia outside of the current work. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

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