Liu Jia, Shi Yuequan, Liu Xiaoyan, Zhang Dongming, Bai Yu, Xu Yan, Wang Mengzhao
Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Dizal Pharmaceutical Co., Ltd., Shanghai 201203, China.
Zhongguo Fei Ai Za Zhi. 2022 Jul 20;25(7):460-467. doi: 10.3779/j.issn.1009-3419.2022.102.24.
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. .
腺苷是在肿瘤微环境中大量产生的一种代谢产物，它通过在免疫细胞上广泛表达的腺苷A2A受体（A2AR）来抑制炎症组织中的免疫反应，从而相应地抑制抗肿瘤免疫反应。因此，阻断腺苷信号通路具有促进抗肿瘤免疫的潜力。本综述简要介绍了腺苷信号通路，描述了其在调节肿瘤免疫中的作用，并强调了A2AR阻断在癌症治疗中的作用。临床前数据已经揭示了腺苷/A2AR抑制的预期抗肿瘤活性，并且多项A2AR拮抗剂的临床试验正在进行中。临床试验的初步结果表明，A2AR拮抗剂在癌症患者中耐受性良好，作为单一疗法或与其他疗法联合使用均有效。未来，寻找预测性生物标志物对于识别最有可能从腺苷通路阻断中获益的患者至关重要，并且需要进一步研究以合理地将A2AR拮抗剂与其他抗肿瘤疗法联合使用。
