肿瘤免疫治疗靶点CD73及其抑制剂研究进展

Research progress of tumor immunotherapy target CD73 and its inhibitors

关键词:  CD73  腺苷  小分子抑制剂  癌症免疫治疗

Key words:  CD73  adenosine  small molecule inhibitors  cancer immunotherapy

摘要:

腺苷(Ado)在多种疾病中具有免疫抑制作用,而细胞表面的胞外-5′-核苷酸酶(CD73)是催化细胞外腺苷生成的限速酶。CD73已被证明在调节性T细胞、B细胞、巨噬细胞和自然杀伤细胞等多种免疫细胞中发挥重要的肿瘤免疫调节作用。在肿瘤微环境(TME)中,CD73介导的腺苷途径在癌症恶化过程中发挥重要的信号传导功能,使CD73成为一种新的免疫检查点。因此,抑制CD73作为新型癌症免疫疗法的前景被广泛看好,目前多种单克隆抗体和小分子抑制剂已处于临床研究阶段。本综述全面总结了CD73小分子抑制剂的研究进展,可为新型CD73抑制剂的开发提供指导。

Abstract:

Adenosine (Ado) has been proved to have immunosuppressive effect in many different diseases, and the activity of ecto-5’-nucleotidase (CD73) on the cell surface is the rate-limiting step of extracellular adenosine production. CD73 has a profound and lasting impact on tumor immune regulation of regulatory T cells (Tregs), B cells, macrophages and natural killer cells. CD73-mediated adenosine pathway is significant in signal transduction during cancer progression in tumor microenvironment (TME), making CD73 a novel immune checkpoint. Therefore, CD73 inhibition is a emergent and promising strategy for cancer immunotherapy. At present, a variety of monoclonal antibodies (mAbs) and small molecule inhibitors have been in clinical development. This review comprehensively summarizes the frontier research progress of reported small molecule CD73 inhibitors, which can provide guidance for the investigation of novel CD73 inhibitors for cancer therapy.