Zhulai G A, Shibaev M I
Institute of Biology, Karelian Research Centre, Russian Academy of Sciences, Petrozavodsk, 185910 Russian Federation.
Endoscopic Department, Baranov Republican Hospital, Petrozavodsk, 185910 Russian Federation.
Acta Naturae. 2023 Apr-Jun;15(2):42-49. doi: 10.32607/actanaturae.11871.
Tumor cells have the capacity to create an adenosine-rich immunosuppressive environment, which can interfere with antitumor immunotherapy. Approaches are currently being developed with a view to suppressing the production of adenosine or its signals. Such approaches include the use of antibodies to inhibit CD39, CD73, and adenosine-receptor antagonists. However, the abundance of enzymatic pathways that control the ATP-adenosine balance, as well as the still poorly understood intracellular adenosine regulation, makes the hoped-for success unlikely. In the present study, the enzyme adenosine kinase (ADK) needed to convert adenosine to adenosine monophosphate, thereby regulating its levels, was investigated. To do so, peripheral blood samples from patients with colorectal cancer (CRC) ( = 31) were collected with blood samples from healthy donors ( = 17) used as controls. ADK gene expression levels and those of its long () and short () isoforms were measured. The relationship between the levels of gene expression and that of , , and genes was analyzed. It turned out that in the group of CRC patients (stages III-IV), the level of mRNA was lower ( < 0.0011) when compared to that of the control. For the first time, an average correlation was found between the level of expression of and ( = -0.468 at = 0.043) and between and ( = 0.518 at = 0.0232) in CRC patients. Flow cytometry was used to assess the content of CD39/CD73-expressing CD8, CD4 and Treg lymphocytes, as well as their relationship with the level of ADK gene expression in CRC patients. But no significant correlations were found.
肿瘤细胞有能力营造一个富含腺苷的免疫抑制环境，这会干扰抗肿瘤免疫疗法。目前正在研发相关方法以抑制腺苷的产生或其信号传导。此类方法包括使用抗体抑制CD39、CD73以及腺苷受体拮抗剂。然而，控制ATP - 腺苷平衡的酶促途径众多，且细胞内腺苷调节仍知之甚少，这使得预期的成功不太可能实现。在本研究中，对将腺苷转化为单磷酸腺苷从而调节其水平所需的腺苷激酶（ADK）进行了研究。为此，收集了31例结直肠癌（CRC）患者的外周血样本，并以17例健康供者的血样作为对照。测量了ADK基因表达水平及其长（）和短（）异构体的表达水平。分析了基因表达水平与、和基因表达水平之间的关系。结果发现，在CRC患者（III - IV期）组中，与对照组相比，mRNA水平较低（<0.0011）。首次在CRC患者中发现与的表达水平之间存在平均相关性（在= 0.043时，= -0.468）以及与之间存在平均相关性（在= 0.0232时，= 0.518）。使用流式细胞术评估CRC患者中表达CD39/CD73的CD8、CD4和调节性T淋巴细胞的含量，以及它们与ADK基因表达水平的关系。但未发现显著相关性。
