Wang Yan, Chen Yuanyuan, Liu Yuanyuan, Zhao Jingjing, Wang Gongming, Chen Hao, Tang Yan, Ouyang Dijun, Xie Songzuo, You Jinqi, Yang Xinyi, Li Minxing, Xia Jianchuan, Xiang Tong, Weng Desheng
Department of Biotherapy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China.
Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, 510630, Guangzhou, China.
Cell Death Dis. 2025 Feb 25;16(1):129. doi: 10.1038/s41419-025-07444-z.
Aberrant vascular systems are significant indicators of cancer and play pivotal roles in tumor immunomodulation. However, the role of PD-L1 expressed on vascular endothelial cells (VECs) in the tumor immune microenvironment of nasopharyngeal carcinoma (NPC), as well as its correlation with patient prognosis, remains unclear. According to in vitro experiments conducted in our research, NPC tumor supernatants could upregulate PD-L1 expression on HUVECs, and the upregulated PD-L1 could bind to PD-1 on T cells leading to diminished T cell killing. The results of animal experiments similarly showed that elevated levels of PD-L1 on tumor VECs hindered the anti-tumor effectiveness of T cells, resulting in immune evasion and tumor progression. Furthermore, PD-L1 expression on tumor VECs served as a valuable prognostic marker, with heightened expression linked to poorer prognosis in NPC patients. Mechanistically, we discovered that the interaction between NF-κB and STAT3 signaling pathways may contribute significantly to the up-regulation of PD-L1 on VECs in NPC. Together, our work provides novel insights into identifying prognostic markers and strategies for reversing immune evasion mechanisms in NPC.
异常血管系统是癌症的重要指标，在肿瘤免疫调节中起关键作用。然而，血管内皮细胞（VECs）上表达的PD-L1在鼻咽癌（NPC）肿瘤免疫微环境中的作用及其与患者预后的相关性仍不清楚。根据我们研究中的体外实验，NPC肿瘤上清液可上调人脐静脉内皮细胞（HUVECs）上的PD-L1表达，上调的PD-L1可与T细胞上的PD-1结合，导致T细胞杀伤能力减弱。动物实验结果同样表明，肿瘤VECs上PD-L1水平升高会阻碍T细胞的抗肿瘤效果，导致免疫逃逸和肿瘤进展。此外，肿瘤VECs上的PD-L1表达是一个有价值的预后标志物，其表达升高与NPC患者预后较差有关。从机制上讲，我们发现NF-κB和STAT3信号通路之间的相互作用可能对NPC中VECs上PD-L1的上调有显著贡献。总之，我们的工作为识别NPC的预后标志物和逆转免疫逃逸机制的策略提供了新的见解。
