Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月30日

查看全文
  • Xiaobing Duan,
  • 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

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.