Lymphocyte activating gene 3 protein expression in nasopharyngeal carcinoma is correlated with programmed cell death-1 and programmed cell death ligand-1, tumor-infiltrating lymphocytes.
Lymphocyte activating gene 3 protein expression in nasopharyngeal carcinoma is correlated with programmed cell death-1 and programmed cell death ligand-1, tumor-infiltrating lymphocytes.
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鼻咽癌中淋巴细胞激活基因3蛋白表达与程序性细胞死亡-1和程序性细胞死亡配体-1、肿瘤浸润淋巴细胞相关
DOI：
10.1186/s12935-021-02162-w
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发表时间：
2021-08-28
影响因子：
5.8
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Luo F;Cao J;Lu F;Zeng K;Ma W;Huang Y;Zhang L;Zhao H
免疫治疗在鼻咽癌（NPC）患者中显示出有希望的疗效。淋巴细胞活化因子3基因（LAG-3）是一个重要的免疫靶点，但其与鼻咽癌的关系尚不清楚。本研究旨在评估LAG-3在NPC中的表达及其与CD 3+肿瘤浸润淋巴细胞（TIL）、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。共182例鼻咽癌患者来自中山大学肿瘤防治中心，中国被纳入这项回顾性研究。采用免疫组化法检测15株NPC细胞系中LAG-3的表达，并检测临床标本中LAG-3、CD 3 + TIL、GZMB、PD-L1和PD-1的表达。卡方检验用于估计LAG-3、其他生物标志物和临床特征之间的关联。采用Kaplan-Meier法和考克斯回归模型进行生存分析。LAG-3在所有15株NPC细胞系中均为阴性表达，而147例（80.8%）NPC患者肿瘤组织中的TIL上显示出高表达LAG-3。男性患者和EBV阳性者LAG-3表达较高。相关性分析显示，LAG-3表达与TIL上的PD-1表达相关，以及肿瘤细胞（TC）和TIL上的PD-L1表达相关。单变量和多变量考克斯模型均表明，病理类型III（P = 0.036）、TIL上LAG-3较高（P < 0.001）、TC上PD-L1较高（P = 0.027）和TIL上PD-1较高（P < 0.001）与无病生存期（DFS）较差相关。然而，仅在单变量考克斯分析中，TIL上较低的PD-L1表达与上级DFS相关（P = 0.002）。TIL上LAG-3和PD-1的高表达、TC上PD-L1的高表达以及病理类型III被确定为NPC患者DFS较差的独立危险因素。我们的数据表明，LAG-3是一种有前途的抑制性受体，可能在抗NPC治疗中发挥重要作用。在线版本包含补充材料，可通过10.1186/s12935-021-02162-w获得。
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. The online version contains supplementary material available at 10.1186/s12935-021-02162-w.
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影响因子：
20.4
作者：
He, Yayi;Yu, Hui;Hirsch, Fred R.
通讯作者：
Hirsch, Fred R.
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