Institute of Biology, Karelian Research Centre, Russian Academy of Sciences, 185910 Petrozavodsk, Russia.
Endoscopic Department, Baranov Republican Hospital, 185019 Petrozavodsk, Russia.
Biomolecules. 2022 Mar 8;12(3):418. doi: 10.3390/biom12030418.
The immunosuppressive effect of adenosine in the microenvironment of a tumor is well established. Presently, researchers are developing approaches in immune therapy that target inhibition of adenosine or its signaling such as CD39 or CD73 inhibiting antibodies or adenosine A2A receptor antagonists. However, numerous enzymatic pathways that control ATP-adenosine balance, as well as understudied intracellular adenosine regulation, can prevent successful immunotherapy. This review contains the latest data on two adenosine-lowering enzymes: adenosine kinase (ADK) and adenosine deaminase (ADA). ADK deletes adenosine by its phosphorylation into 5'-adenosine monophosphate. Recent studies have revealed an association between a long nuclear ADK isoform and an increase in global DNA methylation, which explains epigenetic receptor-independent role of adenosine. ADA regulates the level of adenosine by converting it to inosine. The changes in the activity of ADA are detected in patients with various cancer types. The article focuses on the biological significance of these enzymes and their roles in the development of cancer. Perspectives of future studies on these enzymes in therapy for cancer are discussed.
腺苷在肿瘤微环境中的免疫抑制作用已得到充分证实。目前，研究人员正在开发针对抑制腺苷或其信号转导的免疫治疗方法，如 CD39 或 CD73 抑制抗体或腺苷 A2A 受体拮抗剂。然而，许多控制 ATP-腺苷平衡的酶促途径以及研究较少的细胞内腺苷调节都可能会阻碍免疫治疗的成功。这篇综述包含了两种降低腺苷的酶的最新数据：腺苷激酶 (ADK) 和腺苷脱氨酶 (ADA)。ADK 通过将其磷酸化为 5'-单磷酸腺苷来删除腺苷。最近的研究揭示了长核 ADK 同工型与全球 DNA 甲基化增加之间的关联，这解释了腺苷的表观遗传受体非依赖性作用。ADA 通过将其转化为肌苷来调节腺苷的水平。在各种癌症类型的患者中都检测到 ADA 活性的变化。本文重点介绍了这些酶的生物学意义及其在癌症发展中的作用。还讨论了未来针对这些酶在癌症治疗中的研究前景。
