Memorial Sloan Kettering Cancer Center, New York, NY; Weill Medical College of Cornell University, New York, NY.
Memorial Sloan Kettering Cancer Center, New York, NY; Weill Medical College of Cornell University, New York, NY.
Am J Kidney Dis. 2019 Oct;74(4):529-537. doi: 10.1053/j.ajkd.2019.03.433. Epub 2019 Jul 11.
Immunologic control of malignancy has long been recognized as an important determinant of disease progression. Recent advances in immunology have led to the focus on several mechanisms that can be targeted to achieve tumor suppression. In particular, checkpoint inhibition has evolved in less than a decade to become one of the most important strategies in cancer therapy, with a meaningful improvement in patient survival. Six agents have been approved for clinical use to date and many more are in the industry pipeline. The spectrum of malignancies responsive to immunotherapy ranges from advanced melanoma, for which the first immune checkpoint inhibitor ipilimumab was approved, to Hodgkin lymphoma, non-small cell lung cancer, renal cell carcinoma, and others. Notwithstanding its clinical benefits, checkpoint inhibition carries a risk for significant off-target toxicity stemming from the immune system activation. In this review, we discuss general principles of checkpoint inhibition, mechanisms of toxicity, and kidney complications of the treatment and propose diagnostic and treatment strategies when kidney injury occurs.
免疫控制恶性肿瘤一直被认为是疾病进展的重要决定因素。免疫学的最新进展促使人们关注几种可以靶向以实现肿瘤抑制的机制。特别是,检查点抑制在不到十年的时间内发展成为癌症治疗中最重要的策略之一,患者的生存率有了显著提高。迄今为止,已有六种药物被批准用于临床,还有更多的药物正在研发中。免疫疗法对恶性肿瘤的反应范围从晚期黑色素瘤(第一个免疫检查点抑制剂伊匹单抗就是针对这种疾病批准的)到霍奇金淋巴瘤、非小细胞肺癌、肾细胞癌等。尽管免疫检查点抑制具有临床益处,但由于免疫系统的激活,它也存在着严重的脱靶毒性的风险。在这篇综述中,我们讨论了检查点抑制的一般原则、毒性机制以及治疗相关的肾脏并发症,并提出了发生肾损伤时的诊断和治疗策略。