中国癌症杂志 ›› 2018, Vol. 28 ›› Issue (2): 81-87.doi: 10.19401/j.cnki.1007-3639.2018.02.001

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免疫治疗在膀胱癌中的最新研究进展和未来展望

曹达龙,叶定伟   

  1. 复旦大学附属肿瘤医院泌尿外科,复旦大学上海医学院肿瘤学系,上海 200032
  • 出版日期:2018-02-28 发布日期:2018-03-08
  • 通信作者: 叶定伟 E-mail:dwyeli@163.com

Advances and future prospects of immunotherapy in bladder cancer

CAO Dalong, YE Dingwei   

  1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Published:2018-02-28 Online:2018-03-08
  • Contact: YE Dingwei E-mail: dwyeli@163.com

摘要: 膀胱癌已成为泌尿男生殖系统中常见的恶性肿瘤。自1976年将卡介苗(Bacillus Calmette-Guerin,BCG)膀胱灌注成功地用于非肌层浸润性膀胱癌治疗之后,膀胱癌的治疗未见显著进步,尤其是局部进展和转移性膀胱癌的治疗效果仍不理想。近年来,膀胱癌免疫治疗取得了重大突破,尤其是针对程序性细胞死亡分子1(programmed death-1,PD-1)、程序性细胞死亡分子配体1(programmed death-ligand 1,PD-L1)和细胞毒T淋巴细胞相关蛋白4(cytotoxic T-lymphocyte-associated protein 4,CTLA-4)的免疫检查点抑制剂已被证实不仅具有良好的耐受性,而且能显著改善局部进展和晚期膀胱癌患者的预后。PD-1、PD-L1和CTLA-4抑制剂主要通过阻断负向调控信号,恢复T细胞活性,从而增强T细胞的抗肿瘤免疫应答。其他免疫治疗还包括嵌合抗原受体T细胞免疫疗法(chimeric antigen receptor T-cell immunotherapy,CAR-T)等也具有良好的发展前景。该研究将对免疫治疗在膀胱癌治疗中的作用机制、疗效等进行综述。

关键词: 膀胱癌, 免疫治疗, 卡介苗, PD-1, PD-L1, CTLA-4

Abstract: Bladder cancer is one of the common genitourinary malignancies. Since the discovery of intravesical Bacillus Calmette-Guerin (BCG) in the 1970s for non-muscle invasive bladder cancer, there have not been any major breakthrough drugs especially for locally advanced and metastatic bladder cancer. Recently, the immunotherapy for bladder cancer has made great breakthrough. Immune-checkpoint inhibitors targeting the programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways have shown significant long-term responses and tolerable safety profiles for locally advanced and metastatic bladder cancer. Inhibitors targeting PD-1, PD-L1 and CTLA-4 are mainly used to restore T cell activity by blocking negative regulation signal, and to enhance the anti-tumor activities of T cells. Other immunotherapies including chimeric antigen receptor T-cell (CAR-T) therapy also have great prospects. In this review, the effect of immunotherapeutic agents and the mechanisms in the treatment of bladder cancer are summarized.

Key words: Bladder cancer, Immunotherapy, BCG, PD-1, PD-L1, CTLA-4