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

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2024-10-25 DOI:10.1016/j.esmoop.2024.103961

{"title":"Expression of PD-L1, PD-L2, and inflammatory gene expression profile in locally advanced head and neck squamous cell carcinoma","authors":"","doi":"10.1016/j.esmoop.2024.103961","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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).</div></div><div><h3>Patients and methods</h3><div>PD-L1 and PD-L2 expression on tumor and immune-infiltrating cells (positivity defined as combined positive score or immunohistochemistry proportion score <u>></u>1) and T-cell-inflamed gene expression profile (Tcell<sub>inf</sub>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.</div></div><div><h3>Results</h3><div>Among 366 patients, 38.8% had human papillomavirus-positive disease. PD-L1-positive, PD-L2-positive, and high Tcell<sub>inf</sub>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 (<em>r</em><sub>Spearman</sub> = 0.50), and each biomarker was slightly less correlated with Tcell<sub>inf</sub>GEP (0.41-0.45). PD-L1 expression and high Tcell<sub>inf</sub>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<sub>inf</sub>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).</div></div><div><h3>Conclusion</h3><div>High Tcell<sub>inf</sub>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.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ESMO Open","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2059702924017319","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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_infGEP) 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_infGEP (≤−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_infGEP (0.41-0.45). PD-L1 expression and high Tcell_infGEP 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_infGEP 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_infGEP 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.

查看原文本刊更多论文

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

背景：肿瘤免疫微环境在癌症治疗反应和耐药性中的作用越来越受到关注。这项回顾性研究描述并调查了程序性死亡配体1（PD-L1）、PD-L2和免疫基因表达特征及其与局部晚期头颈部鳞状细胞癌（LA HNSCC）临床预后的关系：对2000年至2015年期间在韩国接受治疗的LA HNSCC患者的肿瘤和免疫浸润细胞上的PD-L1和PD-L2表达（阳性定义为合并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（TcellinfGEP）进行了评估。评估了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系：结果：在366名患者中，38.8%的人乳头瘤病毒阳性。PD-L1阳性、PD-L2阳性和高TcellinfGEP（≤-0.162）状态的患者分别占83.6%、85.4%和73.2%；4.1%为治疗后样本。PD-L1 和 PD-L2 评分之间的相关性为中等（rSpearman = 0.50），每个生物标记物与 TcellinfGEP 的相关性略低（0.41-0.45）。PD-L1 表达和高 TcellinfGEP 状态与人类乳头瘤病毒阳性相关。与其他HNSCC部位相比，口腔癌和口咽癌中所有生物标记物的水平都较高。在同时调整所有三种生物标志物的多变量分析中，只有高TcellinfGEP与较长的总生存期（调整后危险比为0.57；95%置信区间为0.33-0.98）和无复发生存期（调整后危险比为0.41；95%置信区间为0.23-0.74）显著相关：结论：高TcellinfGEP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HNSCC中程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）的疗法有影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.