Department of Oncology, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Am J Transplant. 2020 Aug;20(8):2264-2268. doi: 10.1111/ajt.15856. Epub 2020 Apr 12.
In this report, we describe the first kidney retransplantation performed after anti-programmed cell death-1 (PD-1)-related allograft rejection. In 2014, we administered pembrolizumab (anti-PD-1) for ~9 months to a 57-year-old kidney transplant recipient with metastatic cutaneous squamous cell carcinoma (CSCC). The patient experienced both a complete antitumor response and T cell-mediated allograft rejection requiring reinitiation of hemodialysis. Four-and-a-half years after initiating pembrolizumab, the patient remained without evidence of CSCC relapse and received a kidney transplant from a living-unrelated donor. Ten-and-a-half months after kidney retransplantation, the allograft is functioning well and the patient's CSCC remains in remission. This case illustrates the potential for PD-1 blockade to bring about durable immune-mediated tumor control in chronically immunosuppressed patients, and begins to address the feasibility of kidney retransplantation in patients who have previously received immune checkpoint inhibitor therapy for cancer. Results from this and future cases may help elucidate mechanisms of antitumor immunity and allograft tolerance, and inform updates to transplant decision models. Our report also underscores the need for clinical trials testing novel immunotherapy combinations in solid organ transplant recipients designed to uncouple antitumor and anti-allograft immunity.
在本报告中，我们描述了首例抗程序性细胞死亡蛋白-1（PD-1）相关移植物排斥反应后的肾再移植。2014 年，我们为一名 57 岁患有转移性皮肤鳞状细胞癌（CSCC）的肾移植受者使用了派姆单抗（抗 PD-1）约 9 个月。该患者既经历了完全抗肿瘤反应，也经历了 T 细胞介导的移植物排斥反应，需要重新开始血液透析。在开始使用派姆单抗后 4 年半，患者仍未出现 CSCC 复发的迹象，并接受了来自活体非亲属供者的肾移植。肾再移植后 10 个半月，移植物功能良好，患者的 CSCC 仍处于缓解期。该病例说明了 PD-1 阻断可能在慢性免疫抑制患者中带来持久的免疫介导的肿瘤控制，并开始探讨在先前接受过癌症免疫检查点抑制剂治疗的患者中进行肾再移植的可行性。来自本病例和其他未来病例的结果可能有助于阐明抗肿瘤免疫和移植物耐受的机制，并为移植决策模型的更新提供信息。我们的报告还强调了需要进行临床试验，以测试旨在分离抗肿瘤和抗移植物免疫的新型免疫治疗组合，用于实体器官移植受者。
