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Abstract：
The adenosine pathway is an exciting new target in the field of cancer immunotherapy. CD73 is the main producer of extracellular adenosine. Non-small cell lung cancer (NSCLC) has one of the highest CD73 expression signatures among all cancer types and the presence of common oncogenic drivers of NSCLC, such as mutant epidermal growth factor receptor (EGFR) and KRAS, correlate with increased CD73 expression. Current immune checkpoint blockade (ICB) therapies only benefit a subset of patients, and it has proved challenging to understand which patients might respond even with the current understanding of predictive biomarkers. The adenosine pathway is well known to disrupt cytotoxic function of T cells, which is currently the main target of most clinical agents. Data thus far suggests that combining ICB therapies already in the clinic with adenosine pathway inhibitors provides promise for the treatment of lung cancer. However, antigen loss or lack of good antigens limits efficacy of ICB; simultaneous activation of other cytotoxic immune cells such as natural killer (NK) cells can be explored in these tumors. Clinical trials harnessing both T and NK cell activating treatments are still in their early stages with results expected in the coming years. In this review we provide an overview of new literature on the adenosine pathway and specifically CD73. CD73 is thought of mainly for its role as an immune modulator, however recent studies have demonstrated the tumor cell intrinsic properties of CD73 are potentially as important as its role in immune suppression. We also highlight the current understanding of this pathway in lung cancer, outline ongoing studies examining therapies in combination with adenosine pathway targeting, and discuss future prospects.
摘要：
腺苷途径是癌症免疫治疗领域令人兴奋的新靶点。CD73是细胞外腺苷的主要生产者。非小细胞肺癌（NSCLC）在所有癌症类型中具有最高的CD73表达特征之一，并且存在NSCLC的常见致癌驱动因素。如突变表皮生长因子受体（EGFR）和KRAS，与CD73表达增加相关。当前的免疫检查点阻断（ICB）疗法仅使一部分患者受益。事实证明，即使目前对预测性生物标志物的理解，了解哪些患者可能会做出反应也具有挑战性。众所周知，腺苷途径会破坏T细胞的细胞毒性功能，这是目前大多数临床药物的主要目标。迄今为止的数据表明,已经在临床中的ICB疗法与腺苷途径抑制剂的组合为肺癌的治疗提供了希望。然而,抗原丢失或缺乏良好的抗原限制了ICB的功效;在这些肿瘤中可以探索其他细胞毒性免疫细胞如自然杀伤(NK)细胞的同时激活。利用T和NK细胞活化治疗的临床试验仍处于早期阶段，预计未来几年会有结果。在这篇综述中，我们提供了关于腺苷途径和特别是CD73的新文献的概述。CD73被认为主要是作为免疫调节剂的作用，然而，最近的研究表明，CD73的肿瘤细胞固有特性可能与其在免疫抑制中的作用一样重要。我们还强调了目前对肺癌中这种途径的理解，概述正在进行的研究，检查与腺苷途径靶向结合的疗法，讨论未来的前景。
