《生命科学》 2017, 29(8): 713-721

CTLA-4和PD-1信号通路在实体瘤治疗中的研究进展

左乔竹，覃文新*

(上海交通大学医学院附属仁济医院上海市肿瘤研究所，癌基因及相关基因国家重点实验室，上海 200032)

摘　要：摘　要：细胞毒性T 淋巴细胞相关抗原4 (cytotoxic T-lymphocyte-associated antigen 4， CTLA-4) 和程序性死亡受体1 (programmed death 1， PD-1) 免疫检查点在T 细胞免疫反应中起负性调节作用。通过对这些靶点的抑制，可增强对免疫系统的激活，为黑色素瘤、非小细胞肺癌等提供新的免疫治疗途径。CTLA-4 和PD-1信号通路在免疫反应及抗肿瘤中机制有所不同，针对这两条信号通路的免疫检查点抑制剂也具有不同的效应。现将综述CTLA-4 和PD-1 信号通路的作用机制及相应靶点阻断剂在实体肿瘤免疫治疗中的应用及研究进展。

Progress of CTLA-4 and PD-1 signaling pathways in immunotherapy for human solid cancers

ZUO Qiao-Zhu， QIN Wen-Xin*

(State Key Laboratory of Oncogenes and Related Genes， Shanghai Cancer Institute， Renji Hospital， Shanghai Jiao Tong University School of Medicine， Shanghai 200032， China)

Abstract: Abstract: Immune checkpoints of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) are negative regulators of T-cell immune function. Inhibition of the targets in the two pathways results in increased activation of the immune system and provides novel immunotherapies for melanoma， non-small cell lung cancer， and other human cancers. The roles of CTLA-4 and PD-1 signaling pathways in inhibiting immune response， including antitumor effects， are largely distinct. Clinical outcomes of immune-oncology agents inhibiting the checkpoints in the two pathways may vary based on their differences in mechanism. This article provides an overview of the CTLA-4 and PD-1 pathways and their implications in solid cancer immunotherapy.