腺苷/A2AR信号通路阻断在肿瘤治疗中的应用

Blocking Adenosine/A2AR Pathway for Cancer Therapy

腺苷是一种在肿瘤微环境中高水平产生的代谢产物,主要通过在免疫细胞上表达的腺苷A2A受体(adenosine A2A receptor,A2AR)有效地抑制炎症组织中的免疫反应,抑制抗肿瘤免疫应答。因此阻断腺苷信号通路是促进抗肿瘤免疫的重要方向。在这篇文章中,我们将简介腺苷信号通路,总结腺苷/A2AR在抑制肿瘤免疫中的作用,并介绍腺苷/A2AR通路阻断在抗肿瘤治疗中的研究现状。临床前研究数据已揭示了抑制A2AR治疗肿瘤的潜在效力,A2AR拮抗剂从基础研究向临床应用的转化也正在进行当中。临床试验的初步结果显示,A2AR拮抗剂在肿瘤患者中安全性良好,无论单药还是联合其他疗法使用均有一定的疗效。未来仍需进一步探索如何选取生物标志物对潜在获益人群进行筛选,以及如何联用A2AR拮抗剂和其他治疗方案以实现最优的抗肿瘤策略。

Adenosine is a metabolite produced abundantly in the tumor microenvironment,dampening immune response in inflamed tissues via adenosine A2A receptor(A2AR)which is widely expressed on immune cells,inhibiting anti-tumor immune response accordingly.Therefore,blocking adenosine signaling pathway is of potential to promote anti-tumor immunity.This review briefly introduces adenosine signaling pathway,describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy.Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data,and a number of clinical trials of A2AR antagonists are under way.Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies.In the future,finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade,and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies.