Zhu Qian, Cai Mu-Yan, Chen Chang-Long, Hu Hao, Lin Huan-Xin, Li Min, Weng De-Sheng, Zhao Jing-Jing, Guo Ling, Xia Jian-Chuan
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.
Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.
Oncoimmunology. 2017 Apr 27;6(5):e1312240. doi: 10.1080/2162402X.2017.1312240. eCollection 2017.
Programmed death ligand 1 (PD-L1) expression represents a mechanism of immune escape by inhibiting T cell immunity. This study systematically evaluated the expression of PD-L1, spatial distribution of CD3 immune cells and the relationship of both factors to survival in nasopharyngeal carcinoma (NPC) patients. A total of 209 NPC patients treated between 1991 and 2000 were included. Pairs of TMAs were immunohistochemically stained with PD-L1 and CD3. Survival analysis was evaluated according to PD-L1 status and the spatial distribution of CD3 immune cells in the primary lesion microenvironment. PD-L1 staining was observed on tumor cells and tumor-infiltrating immune cells (TILs); however, PD-L1-positive immune cells were more common (98/209) than PD-L1-positive tumor cells (68/209). Limited numbers of intra-tumoral CD3 T cells (median number: 20) were detected. Patients with higher CD3 T cell infiltration, both intratumorally and peritumorally, had higher PD-L1 expression on tumor cells (both < 0.001) and immune cells ( = 0.002 and < 0.001, respectively). Increasing intratumoral CD3 infiltration was correlated with increased overall survival (OS) ( = 0.008) and disease-free survival (DFS) ( = 0.003). Nevertheless, patients with low levels of peritumoral TILs showed superior OS ( = 0.557) and DFS to those with higher levels of peritumoral TILs ( = 0.671). Moreover, type classification based on intratumoral CD3 infiltration and tumor cell PD-L1 expression was an independent prognostic factor for NPC patients. PD-L1 expression on tumor cells is a favorable prognosis factor in NPC patients with pre-existing intratumor-infiltrating lymphocytes.
程序性死亡配体1（PD-L1）的表达是通过抑制T细胞免疫来实现免疫逃逸的一种机制。本研究系统评估了鼻咽癌（NPC）患者中PD-L1的表达、CD3免疫细胞的空间分布以及这两个因素与生存的关系。纳入了1991年至2000年间接受治疗的209例NPC患者。对成对的组织微阵列（TMAs）进行PD-L1和CD3免疫组化染色。根据PD-L1状态和原发灶微环境中CD3免疫细胞的空间分布进行生存分析。在肿瘤细胞和肿瘤浸润免疫细胞（TILs）上观察到PD-L1染色；然而，PD-L1阳性免疫细胞（98/209）比PD-L1阳性肿瘤细胞（68/209）更常见。检测到肿瘤内CD3 T细胞数量有限（中位数：20）。肿瘤内和肿瘤周围CD3 T细胞浸润较高的患者，肿瘤细胞（均<0.001）和免疫细胞（分别为=0.002和<0.001）上的PD-L1表达更高。肿瘤内CD3浸润增加与总生存期（OS）增加（=0.008）和无病生存期（DFS）增加（=0.003）相关。然而，肿瘤周围TILs水平低的患者的OS（=0.557）和DFS优于肿瘤周围TILs水平高的患者（=0.671）。此外基于肿瘤内CD3浸润和肿瘤细胞PD-L1表达的类型分类是NPC患者的独立预后因素。在已有肿瘤浸润淋巴细胞的NPC患者中，肿瘤细胞上的PD-L1表达是一个有利的预后因素。
