Hong M H, Park S, Vo T, Cho J, Jung H A, Lee S-H, Kim S-H, Zhou H, Chirovsky D, Koh Y W, Yoon S O, Webber A L, Gumuscu B, Cho B C, Ahn M-J
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
ESMO Open. 2024 Nov;9(11):103961. doi: 10.1016/j.esmoop.2024.103961. Epub 2024 Oct 25.
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).
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 (TcellGEP) 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.
Among 366 patients, 38.8% had human papillomavirus-positive disease. PD-L1-positive, PD-L2-positive, and high TcellGEP (≤-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 = 0.50), and each biomarker was slightly less correlated with TcellGEP (0.41-0.45). PD-L1 expression and high TcellGEP 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 TcellGEP 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).
High TcellGEP 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.
肿瘤免疫微环境在癌症治疗反应和耐药性方面的研究日益受到关注。这项回顾性研究对局部晚期头颈部鳞状细胞癌（LA HNSCC）中程序性死亡配体1（PD-L1）、PD-L2以及免疫基因表达特征进行了表征和研究，并探讨了它们与临床结局的关联。
对2000年至2015年在韩国接受治疗的LA HNSCC患者评估肿瘤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（TcellGEP）。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。
在366例患者中，38.8%患有人乳头瘤病毒阳性疾病。分别有83.6%、85.4%和73.2%的患者为PD-L1阳性、PD-L2阳性和高TcellGEP（≤-0.162）状态；4.1%为治疗后样本。PD-L1和PD-L2评分之间的相关性为中等（r = 0.50），且每种生物标志物与TcellGEP的相关性稍低（0.41 - 0.45）。PD-L1表达和高TcellGEP状态与人乳头瘤病毒阳性相关。与其他HNSCC部位相比，口腔癌和口咽癌中所有生物标志物的水平更高。在对所有三种生物标志物进行同时调整的多变量分析中，只有高TcellGEP与更长的总生存期（调整后的风险比，0.57；95%置信区间0.33 - 0.98）和无复发生存期（调整后的风险比，0.41；95%置信区间0.23 - 0.74）显著相关。
在LA HNSCC患者中，高TcellGEP状态而非PD-L1或PD-L2表达与更长的生存期独立相关。该结果可能对评估HNSCC中靶向程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）的疗法具有启示意义。
