Luo Fan, Cao Jiaxin, Lu Feiteng, Zeng Kangmei, Ma Wenjuan, Huang Yan, Zhang Li, Zhao Hongyun
Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, China.
Cancer Cell Int. 2021 Aug 28;21(1):458. doi: 10.1186/s12935-021-02162-w.
Immunotherapy has shown promising efficacy in patients with nasopharyngeal carcinoma (NPC). Lymphocyte activating 3 gene (LAG-3) represents a significant immune target, however, its relationship with NPC remains unclear. This study aimed to evaluate LAG-3 expression in NPC and its association with CD3+ tumor-infiltrating lymphocytes (TILs), Granzyme B (GZMB), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) expression.
A total of 182 patients with NPC from Sun Yat-sen University Cancer Center, China, were included in this retrospective study. LAG-3 expression in 15 NPC cell lines and LAG-3, CD3+ TILs, GZMB, PD-L1 and PD-1 in clinical samples were estimated using immunohistochemistry. The Chi-square test was used to estimate the association between LAG-3, other biomarkers, and clinical characteristics. Survival analysis was performed using the Kaplan-Meier method and the Cox regression model.
LAG-3 was negatively expressed in all of the 15 NPC cell lines, whereas, 147 patients with NPC (80.8%) exhibited high LAG-3 expression on TILs from tumor tissues. Male patients and those who were EBV-positive presented higher LAG-3 expression. Correlation analyses showed that LAG-3 expression was related to PD-1 expression on TILs, as well as, PD-L1 expression on tumor cells (TCs) and TILs. Both the univariate and multivariate Cox models indicated that pathological type III (P = 0.036), higher LAG-3 on TILs (P < 0.001), higher PD-L1 on TCs (P = 0.027), and higher PD-1 on TILs (P < 0.001) were associated with poorer disease-free survival (DFS). However, lower PD-L1 expression on TILs was related to superior DFS only in the univariate Cox analyses (P = 0.002).
Higher LAG-3 and PD-1 on TILs, and higher PD-L1 expression on TCs, and pathological type III were identified as independent risk factors for poorer DFS in NPC patients. Our data demonstrate that LAG-3 is a promising inhibitory receptor that may play an important role in anti-NPC therapy.
免疫疗法在鼻咽癌（NPC）患者中已显示出有前景的疗效。淋巴细胞激活3基因（LAG-3）是一个重要的免疫靶点，然而，其与鼻咽癌的关系仍不清楚。本研究旨在评估LAG-3在鼻咽癌中的表达及其与CD3 +肿瘤浸润淋巴细胞（TILs）、颗粒酶B（GZMB）、程序性死亡配体1（PD-L1）和程序性死亡1（PD-1）表达的相关性。
本回顾性研究纳入了来自中国中山大学肿瘤防治中心的182例鼻咽癌患者。使用免疫组织化学方法评估15种鼻咽癌细胞系中的LAG-3表达以及临床样本中的LAG-3、CD3 + TILs、GZMB、PD-L1和PD-1。采用卡方检验评估LAG-3、其他生物标志物与临床特征之间的相关性。使用Kaplan-Meier法和Cox回归模型进行生存分析。
15种鼻咽癌细胞系中LAG-3均呈阴性表达，然而，147例鼻咽癌患者（80.8%）肿瘤组织中的TILs上LAG-3呈高表达。男性患者和EBV阳性患者的LAG-3表达较高。相关性分析表明，LAG-3表达与TILs上的PD-1表达以及肿瘤细胞（TCs）和TILs上的PD-L1表达相关。单因素和多因素Cox模型均表明，病理III型（P = 0.036）、TILs上较高的LAG-3（P < 0.001）、TCs上较高的PD-L1（P = 0.027）以及TILs上较高的PD-1（P < 0.001）与无病生存期（DFS）较差相关。然而，仅在单因素Cox分析中，TILs上较低的PD-L1表达与较好的DFS相关（P = 0.002）。
TILs上较高的LAG-3和PD-1、TCs上较高的PD-L1表达以及病理III型被确定为鼻咽癌患者DFS较差的独立危险因素。我们的数据表明，LAG-3是一种有前景可抑制的受体，可能在抗鼻咽癌治疗中发挥重要作用。
