Centre de Recherche du Centre, Hospitalier l'Université de Montréal (CRCHUM) et Institut du Cancer de Montréal, Montréal, QC, Canada; Faculté de Pharmacie de l'Université de Montréal, Montréal, QC, Canada.
Centre de Recherche du Centre, Hospitalier l'Université de Montréal (CRCHUM) et Institut du Cancer de Montréal, Montréal, QC, Canada; University of Antwerp, Antwerp, Belgium.
Immunol Lett. 2019 Jan;205:31-39. doi: 10.1016/j.imlet.2018.05.001. Epub 2018 May 24.
The ectonucleotidases CD39 and CD73 are cell surface enzymes that catabolize the breakdown of extracellular ATP into adenosine. As such, they constitute critical components of the extracellular purinergic pathway and play important roles in maintaining tissue and immune homeostasis. With the coming of age of cancer immunotherapy, ectonucleotidases and adenosine receptors have emerged as novel therapeutic targets to enhance antitumor immune responses. With early-phase clinical trials showing promising results, it is becoming increasingly important to decipher the distinct mechanisms-of-action of adenosine-targeting agents, identify patients that will benefit from these agents and rationally develop novel synergistic combinations. Given the broad expression of ectonucleotidases and adenosine receptors, a better understanding of cell-specific roles will also be key for successful implementation of this new generation of immuno-oncology therapeutics. We here review the latest studies on the roles of CD73 and adenosine in cancer with a focus on cell-specific function. We also discuss ongoing clinical trials and future avenues for adenosine-targeting agents.
细胞外核苷酸酶 CD39 和 CD73 是细胞表面的酶，可将细胞外 ATP 的分解代谢为腺苷。因此，它们构成细胞外嘌呤能途径的关键组成部分，并在维持组织和免疫稳态方面发挥重要作用。随着癌症免疫疗法的成熟，细胞外核苷酸酶和腺苷受体已成为增强抗肿瘤免疫反应的新型治疗靶点。随着早期临床试验显示出有希望的结果，越来越有必要破译针对腺苷的药物的独特作用机制，确定将从这些药物中受益的患者，并合理开发新的协同组合。鉴于细胞外核苷酸酶和腺苷受体的广泛表达，更好地了解细胞特异性作用也将是成功实施这新一代免疫肿瘤治疗的关键。在这里，我们综述了 CD73 和腺苷在癌症中的作用的最新研究，重点关注细胞特异性功能。我们还讨论了正在进行的临床试验和针对腺苷的药物的未来发展方向。
