PD-1/PD-L1抑制剂在尿路上皮癌免疫治疗中的研究进展

Clinical research progress of anti-PD-1/PD-L1 immunotherapy in urothelial cancer

局部进展或转移性尿路上皮癌的患者在铂类化疗失败后的治疗手段十分有限。发展新的治疗方法,尤其是针对一线化疗失败后的病例显得尤为重要。程序性死亡分子1(PD-1)/程序性死亡受体配体1(PDL1)、细胞毒性T淋巴细胞相关蛋白4(CTLA-4)免疫抑制剂在包括尿路上皮癌在内的多种肿瘤治疗中取得了较为满意的疗效,与常规化疗相比,安全性和耐受性较好,患者总生存获益明显。Atezolizumab、Avelumab、Durvalumab、Nivolumab和Pembrolizumab为5个获批用于治疗尿路上皮癌的免疫检查点抑制剂,可能将重新定义尿路上皮癌的治疗标准,然而相当比例的尿路上皮癌患者对PD-1/PD-L1通路抑制剂无应答,蛋白水平表达的PD-L1在预测免疫检查点抑制剂的临床疗效存在一定的局限性。本文将对抗PD-1/PD-L1免疫治疗在尿路上皮癌中的研究进展作一综述。

Long-term survival remains poor for patients with advanced urothelial carcinoma that progress after platinum-based chemotherapy,and limited treatment options are available for those patients.Development of novel treatment is quite important especially for patients who failed on first-line chemotherapy.Immune-checkpoint inhibitors targeting the programmed death 1/programmed death-ligand 1(PD-1/PD-L1)and cytotoxic T-lymphocyte-associated protein 4(CTLA-4)pathways have shown significant anti-tumor activity,tolerable safety profiles and survival benefit in a variety of tumors including urothelium carcinoma.Atezolizumab,Avelumab,Durvalumab,Nivolumab and Pembrolizumab are promising PD-1/PD-L1 blockade drugs which might redefine the standard of treatment of urothelial carcinoma.However,a significant proportion of patients with urinary epithelial carcinoma did not respond to PD-1/PD-L1 pathway inhibitors.PD-L1 expression as a biomarker has certain limitations in predicting the clinical efficacy of immunotherapy.This review article describes the advances in immunotherapy of urothelial carcinoma.