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免疫检查点阻断在晚期癌症器官移植患者中的应用:我们能走多远?

Immune checkpoint blockade for organ transplant patients with advanced cancer: how far can we go?

机构信息

Department of Radiation Oncology, Institut Jules Bordet - ULB, Brussels.

Department of Radiation Oncology.

出版信息

Curr Opin Oncol. 2019 Mar;31(2):54-64. doi: 10.1097/CCO.0000000000000505.

Abstract

PURPOSE OF REVIEW

Checkpoint inhibitors (CPIs) provide impressive response rates among immunocompetent patients with various solid tumors. So far, organ transplant recipients have been excluded from clinical studies due to the putative risk of allograft rejection however 48 cases of liver and renal transplant patients treated with CPI were already described in literature.

RECENT FINDINGS

Here we discuss 19 cases of liver and 29 cases of renal transplant patients who received CPI for advanced cancer. Disease control rate [stable disease, complete response (CR) and partial response (PR) together] was 35% (21% for liver and 45% for kidney transplant patients). Graft rejection was seen in 37% of liver and 45% and kidney transplant patients. Significantly, our analysis shows that an 'ideal' response occurs in 21% of all patients (antitumor response accompanied with durable graft tolerance).

SUMMARY

We believe that transplant patients can be treated with CPI in a controlled setting and for well informed patients. To obtain a durable antitumor immune response while avoiding rejection, to be able to adjust immunosuppression and to have the opportunity to develop biomarkers for tumor response and transplant rejection, these patients should be treated according to a clinical care path or a prospective clinical trial.

摘要

目的综述

检查点抑制剂(CPIs)在各种实体瘤免疫功能正常的患者中提供了令人印象深刻的反应率。到目前为止,由于同种异体移植排斥的潜在风险,器官移植受者被排除在临床试验之外,然而,文献中已经描述了 48 例接受 CPI 治疗的肝和肾移植患者。

最近的发现

在这里,我们讨论了 19 例肝移植和 29 例肾移植患者,他们因晚期癌症接受了 CPI 治疗。疾病控制率(稳定疾病、完全缓解[CR]和部分缓解[PR]总和)为 35%(肝移植患者为 21%,肾移植患者为 45%)。肝移植和肾移植患者分别有 37%和 45%发生移植物排斥。值得注意的是,我们的分析表明,所有患者中有 21%(抗肿瘤反应伴有持久的移植物耐受)出现“理想”反应。

总结

我们认为,在可控环境下,可以为有充分知情的移植患者使用 CPI。为了获得持久的抗肿瘤免疫反应而避免排斥,能够调整免疫抑制,并有机会开发用于肿瘤反应和移植排斥的生物标志物,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。

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