癌症的发展与免疫抑制性肿瘤微环境（TME）密切相关，这种微环境会削弱抗肿瘤免疫反应并促进肿瘤细胞免疫逃逸。细胞表面上的两个重要核苷酸酶CD39和CD73将细胞外ATP顺序转化为腺苷，发挥重要作用，重塑免疫抑制性TME。积累的细胞外腺苷通过与四种腺苷受体之一（A1R、A2AR、A2BR和A3R）结合介导其调节功能。A2AR通过调节 cAMP信号传导发挥其深刻的免疫抑制功能。越来越多的证据表明，CD39、CD73和A2AR可以作为新的治疗靶点，用于调控抗肿瘤免疫力。近年来，以CD39 / CD73 / A2AR通路为靶点的单克隆抗体或小分子抑制剂已作为单一剂量或与 PD-1 / PD-L1 抗体复合疗法进行临床试验。在本文中，我们对腺苷通路在癌症发展、转移和药物耐药中的病理生理功能进行更新总结，并讨论了以一种或多种腺苷通路成分为靶点的癌症治疗和免疫疗法抵抗规避。并且，本文讨论了新兴的生物标志物，可能被用于指导CD39 / CD73 / A2AR靶向治疗策略的选择。© 2023。作者。

Cancer development is closely associated with immunosuppressive tumor microenvironment (TME) that attenuates antitumor immune responses and promotes tumor cell immunologic escape. The sequential conversion of extracellular ATP into adenosine by two important cell-surface ectonucleosidases CD39 and CD73 play critical roles in reshaping an immunosuppressive TME. The accumulated extracellular adenosine mediates its regulatory functions by binding to one of four adenosine receptors (A1R, A2AR, A2BR and A3R). The A2AR elicits its profound immunosuppressive function via regulating cAMP signaling. The increasing evidence suggests that CD39, CD73 and A2AR could be used as novel therapeutic targets for manipulating the antitumor immunity. In recent years, monoclonal antibodies or small molecule inhibitors targeting the CD39/CD73/A2AR pathway have been investigated in clinical trials as single agents or in combination with anti-PD-1/PD-L1 therapies. In this review, we provide an updated summary about the pathophysiological function of the adenosinergic pathway in cancer development, metastasis and drug resistance. The targeting of one or more components of the adenosinergic pathway for cancer therapy and circumvention of immunotherapy resistance are also discussed. Emerging biomarkers that may be used to guide the selection of CD39/CD73/A2AR-targeting treatment strategies for individual cancer patients is also deliberated.© 2023. The Author(s).