PD-L1、PD-L2 的表达及炎症基因表达谱在局部晚期头颈部鳞状细胞癌中的研究

英文原题：Expression of PD-L1, PD-L2, and inflammatory gene expression profile in locally advanced head and neck squamous cell carcinoma.

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Expression of PD-L1, PD-L2, and inflammatory gene expression profile in locally advanced head and neck squamous cell carcinoma.

PubMed 2024/10/25（内容时间） ESMO Open Q1 · IF 10.6（JCR 2025）

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头颈部鳞癌地区：韩国

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研究概要

高 Tcell inf GEP 状态，而非 PD-L1 或 PD-L2 表达，与 LA HNSCC 患者更长的生存期独立相关。结果可能对评估针对程序性细胞死亡蛋白 1（PD-1）/程序性死亡配体 1（PD-L1）的疗法在 HNSCC 中的应用具有意义。

研究思路结论见上方概要

背景

肿瘤免疫微环境在癌症治疗反应和耐药性中日益受到关注。这项回顾性研究对局部晚期头颈部鳞状细胞癌（LA HNSCC）中的程序性死亡配体1（PD-L1）、PD-L2及免疫基因表达特征进行了表征和探究，并分析了它们与临床结局的关联。

方法

在2000年至2015年间于韩国接受治疗的LA HNSCC患者中，评估了肿瘤细胞和免疫浸润细胞上的PD-L1和PD-L2表达（阳性定义为联合阳性评分或免疫组化比例评分>1）以及T细胞炎症基因表达谱（Tcell inf GEP）。评估了这三种生物标志物之间的相关性及其与总生存期和无复发生存期的关联。

结果

在366例患者中，38.8%为人乳头瘤病毒阳性疾病。PD-L1阳性、PD-L2阳性和高Tcell inf GEP（≤-0.162）状态分别在83.6%、85.4%和73.2%的患者中观察到；4.1%为治疗后样本。PD-L1与PD-L2评分之间呈中度相关（r Spearman = 0.50），且每个生物标志物与Tcell inf GEP的相关性略低（0.41-0.45）。PD-L1表达和高Tcell inf GEP状态与人乳头瘤病毒阳性相关。与其他HNSCC部位相比，口腔癌和口咽癌中观察到所有生物标志物水平更高。在一项同时调整所有三种生物标志物的多变量分析中，只有高Tcell inf GEP与更长的总生存期（调整风险比，0.57；95%置信区间0.33-0.98）和无复发生存期（调整风险比，0.41；95%置信区间0.23-0.74）显著相关。

展开英文摘要原文

BACKGROUND

The tumor immune microenvironment in cancer treatment response and resistance is of increasing interest. This retrospective study characterized and investigated programmed death-ligand 1 (PD-L1), PD-L2, and the immune gene expression signature and their association with clinical outcomes in locoregionally advanced head and neck squamous cell carcinoma (LA HNSCC).

PATIENTS AND METHODS

PD-L1 and PD-L2 expression on tumor and immune-infiltrating cells (positivity defined as combined positive score or immunohistochemistry proportion score >1) and T-cell-inflamed gene expression profile (Tcell inf GEP) were evaluated in patients with LA HNSCC treated in South Korea from 2000 to 2015. Correlations among the three biomarkers and their associations with overall survival and recurrence-free survival were assessed.

RESULTS

Among 366 patients, 38.8% had human papillomavirus-positive disease. PD-L1-positive, PD-L2-positive, and high Tcell inf GEP (≤-0.162) status were observed in 83.6%, 85.4%, and 73.2% of patients, respectively; 4.1% were posttreatment samples. Correlation between PD-L1 and PD-L2 scores was moderate (r Spearman = 0.50), and each biomarker was slightly less correlated with Tcell inf GEP (0.41-0.45). PD-L1 expression and high Tcell inf GEP status were associated with human papillomavirus positivity. Higher levels of all biomarkers were observed in oral cavity and oropharyngeal cancers compared with other HNSCC sites. In a multivariable analysis that simultaneously adjusted for all three biomarkers, only high Tcell inf GEP was significantly associated with longer overall survival (adjusted hazard ratio, 0.57; 95% confidence interval 0.33-0.98) and recurrence-free survival (adjusted hazard ratio, 0.41; 95% confidence interval 0.23-0.74).

CONCLUSION

High Tcell inf GEP status, but not PD-L1 or PD-L2 expression, was independently associated with longer survival in patients with LA HNSCC. Results may have implications for evaluating therapies targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) in HNSCC.

论文信息

作者: Hong MH、Park S、Vo T、Cho J、Jung HA、Lee SH、Kim SH、Zhou H
第一作者单位: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul.South Korea
通讯作者单位: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: silkahn@skku.edu.South Korea
期刊: ESMO open2024 Nov

原文标识: PubMed 39461260　·　DOI 10.1016/j.esmoop.2024.103961

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