PD-1/PD-L1信号通路在恶性肿瘤免疫治疗中的作用

Role of PD-1/PD-L1 signaling pathway in immune treatment of malignant tumors

恶性肿瘤是目前一组严重威胁人类健康和生命的疾病,其发病率和死亡率有不断上升的趋势。免疫治疗是除手术、化疗、放疗之外一项重要的抗肿瘤治疗方式,它可通过刺激机体免疫系统提高抗肿瘤免疫效应。程序性死亡分子1(PD-1)和程序性死亡分子1配体(PD-L1)这两个免疫检查分子,通过抑制T细胞免疫与肿瘤的发生、发展密切相关,目前在部分恶性肿瘤即黑色素瘤、非小细胞肺癌(NSCLC)、肾癌、膀胱癌治疗中有重要临床意义。PD-1/PD-L1信号通路的激活可降低T细胞的免疫功能从而使肿瘤发生免疫逃逸,而阻断此通路则可以增强机体内源性的抗肿瘤免疫效应。目前临床试验显示免疫检查点阻滞剂抗PD-1、抗PD-L1抗体在肿瘤免疫治疗中有较好的疗效性及安全性。本综述旨在回顾及总结近年来PD-1/PD-L1信号通路及其阻滞剂在部分恶性肿瘤治疗中的研究进展。

Malignancy is a group of diseases which have serious threat to human health and in recent years its morbid- ity and mortality has a rising trend. Immunotherapy is an important way of anti-tumor therapy, in addition to surgery, chemotherapy and radiotherapy. It can stimulate the body＇s immune system to improve the anti-tumor immune effects. Study had been reported that immune checkpoint molecules, including programmed death-1 （PD-1）/PD-ligand （L） 1 axis, are closely related with cancer generation and development, by inhibiting T cell immune and play a key role on clinical significance of malignancy, including Melanoma Non-small cell lung cancer （NSCLC）, Renal cell carcinoma （RCC）, Bladder cancer. Activation of PD-1/PD-L1 pathway contributes to tumor immune escape, and block PD-1/PD- L1 pathway can enhance endogenous antimuor immunity. Currently increasing clinical trials suggested that immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 monoclonal antibodies turned out to be beneficial and safe in malignancy. This artical provides a review on the progress of PD-1/PD-L1 pathway and immune checkpoint inhibitors in some malignancy.