Fiedler Mathias, Off Alisa, Gärtner Andreas, Brockhoff Gero, Eichberger Jonas, Gottsauner Maximilian, Schuderer Johannes G, Maurer Michael, Bauer Richard J, Gerken Michael, Reichert Torsten E, Ettl Tobias, Weber Florian
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany.
Institute of Pathology, University of Regensburg, Regensburg, Germany.
Head Neck. 2025 Mar;47(3):822-831. doi: 10.1002/hed.27981. Epub 2024 Oct 27.
This study aimed to explore the disparities in PD-1 and PD-L1 expression among oral squamous cell carcinomas (OSCCs) in individuals categorized as never-smokers/never-drinkers versus smokers/drinkers.
Immunohistochemical staining for PD-1 and PD-L1, along with PDCD1LG2/cen9 dual color probe analysis, was conducted on 130 OSCC specimens from both smoker/drinker and never-smoker/never-drinker cohorts. Associations between smoking/drinking status, clinicopathologic data, immunohistochemical antibody expression, fluorescence in situ hybridization, and survival outcomes were assessed.
OSCC in never-smokers/never-drinkers exhibited significantly elevated PD-1 expression (p = 0.003), increased PD-L1-TPS expression (p = 0.044), and elevated PD-L1-CPS expression (p < 0.001). High PD-L1-ICS expression was more prevalent in never-smokers (p = 0.042). Moreover, never-smokers and never-drinkers demonstrated augmented PD-L1 gene copy numbers (p = 0.081 and p = 0.054, respectively). Increased PD-L1 gene copy number, particularly amplification, correlated with PD-L1-TPS (p = 0.039 and p < 0.001). Conversely, PD-L1 gene copy loss was associated with negative PD-L1-CPS (p = 0.023). Notably, positive PD-L1-CPS was significantly linked with improved overall survival (p = 0.023).
OSCC arising in never-smokers/never-drinkers exhibit heightened PD-1/PD-L1 signaling, suggesting potential efficacy of immune checkpoint therapy in this subgroup of tumors.
本研究旨在探讨从不吸烟者/从不饮酒者与吸烟者/饮酒者中口腔鳞状细胞癌（OSCC）之间程序性死亡受体1（PD-1）和程序性死亡配体1（PD-L1）表达的差异。
对来自吸烟者/饮酒者和从不吸烟者/从不饮酒者队列的130例OSCC标本进行PD-1和PD-L1免疫组织化学染色，以及程序性死亡配体2（PDCD1LG2）/9号染色体着丝粒（cen9）双色探针分析。评估吸烟/饮酒状态、临床病理数据、免疫组织化学抗体表达、荧光原位杂交和生存结果之间的关联。
从不吸烟者/从不饮酒者中的OSCC表现出显著升高的PD-1表达（p = 0.003）、增加的PD-L1肿瘤比例评分（TPS）表达（p = 0.044）和升高的PD-L1综合阳性评分（CPS）表达（p < 0.001）。高PD-L1免疫细胞化学评分（ICS）表达在从不吸烟者中更普遍（p = 0.042）。此外，从不吸烟者和从不饮酒者显示出增加的PD-L1基因拷贝数（分别为p = 0.081和p = 0.054）。PD-L1基因拷贝数增加，特别是扩增，与PD-L1-TPS相关（p = 0.039和p < 0.001）。相反，PD-L1基因拷贝丢失与阴性PD-L1-CPS相关（p = 0.023）。值得注意的是，阳性PD-L1-CPS与改善的总生存期显著相关（p = 0.023）。
从不吸烟者/从不饮酒者中发生的OSCC表现出增强的PD-1/PD-L1信号传导，表明免疫检查点疗法在该肿瘤亚组中具有潜在疗效。
