Adenosine signaling through A2AR serves as a negative regulator of the immune system. Unique to this suppressive pathway is its ability to impact numerous stromal and immune cells. Additionally, tumors exhibit elevated concentrations of adenosine further advancing the pathway's potential as a powerful target for activating anti-tumor immunity. The promise of this therapeutic strategy has been repeatedly demonstrated in mice, but has so far only yielded limited success in the clinic. Nonetheless, it is notable that many of these observed clinical responses have been in individuals resistant to prior immunotherapy. These observations suggest this pathway is indeed involved in tumor immune evasion. Thus, identifying the disparities between the translational and clinical implementation of this therapy becomes necessary. To this end, this review will revisit how and where adenosine-A2AR signaling regulates the immune system and anti-tumor immunity so as to reveal opportunities for improving the translational success of this immunotherapy.

中文翻译：

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重新思考腺苷-A2AR 检查点：对增强抗肿瘤免疫治疗的影响。

通过 A2AR 的腺苷信号传导是免疫系统的负调节因子。这种抑制途径的独特之处在于它能够影响众多基质细胞和免疫细胞。此外，肿瘤表现出升高的腺苷浓度，进一步提高了该途径作为激活抗肿瘤免疫的强大目标的潜力。这种治疗策略的前景已在小鼠身上反复证明，但迄今为止仅在临床上取得了有限的成功。尽管如此，值得注意的是，许多这些观察到的临床反应发生在对先前免疫疗法有抵抗力的个体中。这些观察结果表明该途径确实参与了肿瘤免疫逃避。因此，有必要确定这种疗法的转化和临床实施之间的差异。为此，