Article record

EBV劫持CD73的代谢功能以抵抗NK细胞的抗肿瘤功能。

EBV hijacks the metabolic function of CD73 to resist the antitumor function of NK cells.

基础研究鼻咽癌IF 9.6Q1

文献信息

PMID	42844288
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	Xiaobing Duan 查看其他 19 位作者 Jiali Hu；Shuo Wan；Qiong Luo；Yuncong Zhang；Guangyong Feng；Miaoshan Luo；Zhen Lin；Pei Yu；Hongyun Jia；Jinmei Li；Minhong Wang；Zhongying Wang；Mingxiao Chen；Xinfeng Yang；Meifang Lin；Siyu Li；Tong Xiang；Qiang Zhou；Guihai Zhang
作者单位	Clinical Laboratory Medicine Department, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, PR China. duanxb3@alumni.sysu.edu.cn. 查看其他 11 条单位信息 Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, PR China. duanxb3@alumni.sysu.edu.cn.；Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, PR China.；International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, School of Medicine, Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, PR China.；Department of Oncology, Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai, PR China.；The Second Affiliated Hospital of Zunyi Medical University, Zunyi, PR China.；School of Basic Medical Science, Guangzhou Medical University, Guangzhou, PR China.；Clinical Laboratory Medicine Department, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, PR China.；Department of Oncology, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, PR China.；Department of Experimental Research, 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, Guangzhou, PR China. xiangtong@sysucc.org.cn.；Clinical Laboratory Medicine Department, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, PR China. 2008690871@gzhmu.edu.cn.；Department of Oncology, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, PR China. ghzhang@ext.jnu.edu.cn.
期刊	NPJ precision oncology
SCI 分区	Q1
IF	9.6
研究类型	基础研究 · 基础／转化
所属专科	鼻咽癌

中文摘要

CD73是一种代谢免疫检查点，调节肿瘤微环境（TME）中腺苷水平的稳态平衡。然而，EBV相关恶性肿瘤中CD73异常表达的调控机制仍不清楚。在本研究中，我们证明CD73在EBV相关恶性肿瘤中上调，并与NK细胞的抗肿瘤活性呈负相关。机制上，EBV潜伏蛋白LMP2A通过PI3K/AKT信号通路上调CD73，而CD73的代谢产物腺苷通过多条信号通路负向调控NK细胞的抗肿瘤功能。此外，靶向敲除CD73、小分子抑制剂或中和抗体联合NK细胞过继转移显著提高了EBV阳性鼻咽癌（NPC）的治疗效果。重要的是，我们还发现CD73在EBV阳性淋巴瘤、胃癌和肺癌中异常上调。总之，我们的研究揭示了EBV相关恶性肿瘤中通过CD73异常表达实现NK细胞抗肿瘤功能免疫逃逸的机制，靶向CD73联合NK细胞过继转移可能为EBV相关恶性肿瘤的免疫治疗提供新策略。

英文摘要

CD73 is a metabolic immune checkpoint that regulates the homeostatic balance of adenosine levels in the tumor microenvironment (TME). However, the regulation of CD73 abnormal expression in Epstein-Barr virus (EBV)-associated malignancies remains unclear. In this study, we demonstrate that CD73 is upregulated in EBV-associated malignancies and is negatively correlated with the anti-tumor activity of NK cells. Mechanistically, EBV latent protein LMP2A upregulates CD73 through the PI3K/AKT signaling pathway, and the metabolic product of CD73, adenosine, negatively regulates the anti-tumor function of NK cells through multiple signaling pathways. Furthermore, targeted knockout of CD73, a small molecule inhibitor, or neutralizing antibody combined with the adoptive transfer of NK cells significantly improved the treatment efficacy for EBV-positive nasopharyngeal carcinoma (NPC). Importantly, we also found abnormal upregulation of CD73 in EBV-positive lymphoma, gastric cancer, and lung cancer. In summary, our research identifies the mechanism of immune evasion of NK cell anti-tumor function in EBV-associated malignancies through the abnormal expression of CD73, and targeting CD73 combined with the adoptive transfer of NK cells may provide a new strategy for immunotherapy of EBV-related malignancies.