Feng Li-Li, Cai Yi-Qing, Zhu Ming-Chen, Xing Li-Jie, Wang Xin
1Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong First Medical University, Jinan, 250021 Shandong China.
5Department of Clinical Laboratory, Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital, Nanjing, 210009 Jiangsu China.
Cancer Cell Int. 2020 Apr 7;20:110. doi: 10.1186/s12935-020-01195-x. eCollection 2020.
Extracellular adenosine triphosphate (eATP) and its main metabolite adenosine (ADO) constitute an intrinsic part of immunological network in tumor immunity. The concentrations of eATP and ADO in tumor microenvironment (TME) are controlled by ectonucleotidases, such as CD39 and CD73, the major ecto-enzymes expressed on immune cells, endothelial cells and cancer cells. Once accumulated in TME, eATP boosts antitumor immune responses, while ADO attenuates immunity against tumors. eATP and ADO, like yin and yang, represent two opposite aspects from immune-activating to immune-suppressive signals. Here we reviewed the functions of eATP and ADO in tumor immunity and attempt to block eATP hydrolysis, ADO formation and their contradictory effects in tumor models, allowing the induction of effective anti-tumor immune responses in TME. These attempts documented that therapeutic approaches targeting eATP/ADO metabolism and function may be effective methods in cancer therapy.
细胞外三磷酸腺苷（eATP）及其主要代谢产物腺苷（ADO）构成了肿瘤免疫中免疫网络的固有组成部分。肿瘤微环境（TME）中eATP和ADO的浓度受外切核苷酸酶控制，如CD39和CD73，它们是免疫细胞、内皮细胞和癌细胞表达的主要外切酶。一旦在TME中积累，eATP会增强抗肿瘤免疫反应，而ADO会减弱对肿瘤的免疫反应。eATP和ADO如同阴阳两极，代表了从免疫激活信号到免疫抑制信号的两个相反方面。在此，我们综述了eATP和ADO在肿瘤免疫中的功能，并试图在肿瘤模型中阻断eATP水解、ADO形成及其矛盾效应，从而在TME中诱导有效的抗肿瘤免疫反应。这些尝试证明，针对eATP/ADO代谢和功能的治疗方法可能是癌症治疗的有效手段。
