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免疫检查点抑制剂治疗后肝移植物排斥反应:综述。

Liver graft rejection following immune checkpoint inhibitors treatment: a review.

机构信息

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Wangfujing, Beijing, 100730, China.

出版信息

Med Oncol. 2019 Oct 11;36(11):94. doi: 10.1007/s12032-019-1316-7.

Abstract

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a variety of solid tumors; nonetheless, they have not been well investigated and are still recognized as a relative contraindication for patients with a liver transplantation (LT) history, since ICIs treatment might potentially lead to graft rejection. The program death-1 (PD-1) and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways are implicated in the tolerance of transplanted organ, as well as blockade of the pathways, which contribute to eliminating tumors and may inadvertently lead to peripheral transplant rejection. Currently, no guidelines are available regarding the treatment for ICIs patients with a prior LT history. Therefore, this study was carried out to review the recent studies, attempting to introduce the ICIs-related graft rejection after LT from various aspects. We believed that ICIs could be given for the well-informed patients receiving LT and developed recurrence in a controlled setting. Typically, these patients should be treated according to a clinical care path or a prospective clinical trial, so as obtain a persistent anti-tumor immune response in the meantime of avoiding graft rejection, adjust the immunosuppression, reduce the possibility of graft loss following rejection, and have the opportunity to develop biomarkers for tumor response and transplant rejection.

摘要

免疫检查点抑制剂(ICIs)在多种实体肿瘤中显示出显著的疗效;然而,由于 ICI 治疗可能导致移植物排斥,它们在有肝移植(LT)病史的患者中尚未得到充分研究,仍被认为是相对禁忌证。程序性死亡受体-1(PD-1)和细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)途径参与移植器官的耐受,以及阻断这些途径有助于消除肿瘤,但也可能无意中导致外周移植物排斥。目前,对于有 LT 病史的 ICI 患者的治疗尚无指南。因此,本研究旨在回顾最近的研究,试图从多个方面介绍 LT 后与 ICI 相关的移植物排斥。我们认为,对于知情的 LT 接受者和在可控环境中复发的患者,可以给予 ICI。通常,这些患者应根据临床护理路径或前瞻性临床试验进行治疗,以在避免移植物排斥的同时获得持续的抗肿瘤免疫反应,调整免疫抑制,降低排斥后移植物丢失的可能性,并有可能开发出用于肿瘤反应和移植排斥的生物标志物。

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