Immune Checkpoint Inhibitors and the Risk of Allograft Rejection: A Comprehensive Analysis on an Emerging Issue
Immune Checkpoint Inhibitors and the Risk of Allograft Rejection: A Comprehensive Analysis on an Emerging Issue
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DOI：
10.1634/theoncologist.2018-0195
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发表时间：
2019-03-01
期刊：
影响因子：
5.8
通讯作者：
Hurley, Judith
中科院分区：
文献类型：
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作者：
Aguirre, Luis E.;Guzman, Maria E.;Hurley, Judith
背景众所周知，广泛的免疫抑制诱导的免疫耐受状态，以防止同种异体移植排斥反应导致癌症的发展风险增加。癌症治疗最有前途的新领域之一是开发免疫检查点抑制剂，其靶向细胞毒性T淋巴细胞相关抗原4和程序性细胞死亡蛋白1/程序性死亡配体1（PD-L1）途径。作为一个合乎逻辑的结果，对这些药物的兴趣越来越大，转化为移植相关恶性肿瘤患者的实施。由于移植免疫抑制和癌症免疫调节的作用机制相互重叠，甚至相互排斥，因此研究这些相互作用至关重要。材料和方法我们使用三个引擎对2014年7月至2017年11月期间发表的综述文章和病例报告进行了系统检索：Usearch，PubMed和Up-to-date。结果20例共发生排斥反应12例。与纳武单抗相关的排斥率为73%（8/11），与派姆单抗相关的排斥率为100%（2/2）。使用易普利姆玛在任何情况下均未导致排斥反应（0/4，0%）。在接受依匹单抗/纳武单抗序贯治疗的两名患者中，一名患者失去了同种异体移植物，排斥率为50%。依匹单抗/派姆单抗的顺序使用导致100%的排斥率（1/1，100%）。结论：由于不可接受的高不可逆同种异体移植排斥反应率，在实体器官移植中禁用作用于PD-L1通路的药物。由于机制与PD-L1药物不同，使用易普利姆玛似乎可以耐受。
Background It is well known that the state of immune tolerance induced by broad immunosuppression to prevent allograft rejection leads to an increased risk of the development of cancer. One of the most promising new areas of cancer treatment has been the development of immune checkpoint inhibitors that target the cytotoxic T-lymphocyte-associated antigen 4 and programmed cell death protein 1/programmed death-ligand 1 (PD-L1) pathways. As a logical consequence, growing interest in these agents translated into their implementation in patients with transplant-related malignancies. Because of overlapping and perhaps mutually exclusive mechanisms of action of transplant immunosuppression and cancer immunomodulation, it is critical to examine these interactions. Materials and Methods We carried out a systematic search for review articles and case reports published between July 2014 and November 2017 using three engines: Usearch, PubMed, and Up-to-date. Results Overall, there were 20 cases with 12 allograft rejections. The rejection rate associated with nivolumab was 73% (8/11) and with pembrolizumab it was 100% (2/2). The use of ipilimumab did not lead to rejection in any instance (0/4, 0%). Of the two patients treated with the sequential use of ipilimumab/nivolumab, one lost his allograft, yielding a rejection rate of 50%. The sequential use of ipilimumab/pembrolizumab led to a rejection rate of 100% (1/1, 100%). Conclusion The use of agents that act on the PD-L1 pathway are contraindicated in the face of solid organ allografts because of unacceptably high rates of irreversible allograft rejection. It appears that the use of ipilimumab may be tolerated as the mechanism is different from that of the PD-L1 agents.