Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, USA.
Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, USA.
J Mol Med (Berl). 2018 Sep;96(9):903-913. doi: 10.1007/s00109-018-1679-9. Epub 2018 Aug 1.
Purinergic signaling through adenosine plays a key role in immune regulation. Hypoxia-driven accumulation of extracellular adenosine results in the generation of an immunosuppressive niche that fuels tumor development. Such immunometabolic modulation has shown to be a promising therapeutic target through blockade of adenosine receptors which mediate adenosine's immunosuppressive function, or cancer-associated ectonucleotidases CD39 and CD73 that catalyze the synthesis of adenosine. Adenosinergic signaling heavily implicates natural killer cells through both direct and indirect effects on their cytolytic activity, expression of cytotoxic granules, interferon-γ, and activating receptors. Continuing work has uncovered multiple checkpoints linked to adenosine within the purinergic signaling cascade as contributing to immune evasion from NK cell effector function. Here, we discuss these checkpoints and the recent body of work that focuses on adenosinergic signaling as a target for natural killer cell of cancer.
嘌呤能信号通过腺苷在免疫调节中起着关键作用。缺氧驱动的细胞外腺苷积累导致产生免疫抑制小生境，从而促进肿瘤发展。这种免疫代谢调节已被证明是一种有前途的治疗靶点，通过阻断腺苷受体来介导腺苷的免疫抑制功能，或通过催化腺苷合成的肿瘤相关胞外核苷酸酶 CD39 和 CD73。通过对自然杀伤细胞的细胞毒性活性、细胞毒性颗粒、干扰素-γ和激活受体的直接和间接影响，腺苷能信号强烈牵连自然杀伤细胞。不断的研究揭示了嘌呤能信号级联中的多个与腺苷相关的检查点，这些检查点有助于自然杀伤细胞逃避效应功能。在这里，我们讨论这些检查点以及最近的研究工作，重点关注作为癌症自然杀伤细胞靶点的腺苷能信号。
