Background

Solid organ transplantation (SOT) is a treatment method for end-stage organ diseases and improve their life quality, while using long-term immunosuppressant drugs (ISD) is needed to suppress the function of the immune system. Immune checkpoint inhibitors (ICIs) are a class of anti-tumor drugs that kill tumors by activating the autoimmune system. The primary objective of our systematic review is to investigate the risk factors for organ rejection and the efficacy of ICIs in solid organ transplantation recipients (SOTRs).

Methods

We searched four databases to find relevant articles up to January 2021. A total of 61 articles involving 106 SOTRs met the screening criteria and were included in our systematic review. The collected data were statistical described, and the risk factors were analyzed by logistic regression.

Results

Forty-four patients (41.5%) developed host-versus-graft response (HVGR) after ICIs. mTOR inhibitors (pre-ICIs) (p = 0.069, OR = 0.377, 95% CI 0.132–1.078) and calcineurin inhibitors (post-ICIs) (p = 0.056, OR = 0.375, 95%CI 0.137–1.025) may help reduce the incidence of HVGR. Hormones (pre-ICIs) (p = 0.026, OR = 3.150, 95%CI 1.150–8.628) and anti-metabolites (pre-ICIs) (p = 0.022, OR = 3.214, 95%CI 1.185–8.720) may adversely affect the efficacy of ICIs. Only 35.6% of patients both responded well to ICIs treatment and did not develop HVGR.

Conclusions

Our systematic review summarizes the use of ICIs in SOTRs and evaluates the efficacy of ICIs and the risk factors that induce HVGR. Through risk factor analysis, we found that mTOR inhibitors and calcineurin inhibitors may help to reduce the occurrence of HVGR; hormones and anti-metabolic drugs may have adverse effects on the efficacy of ICIs. In addition, there is a contradictory relationship between the occurrence of HVGR and the efficacy of ICIs.

中文翻译：

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免疫检查点抑制剂在实体器官移植受者中的应用：系统评价

背景

实体器官移植（SOT）是一种治疗终末期器官疾病并改善其生活质量的方法，同时需要使用长期免疫抑制剂（ISD）来抑制免疫系统的功能。免疫检查点抑制剂（ICIs）是一类通过激活自身免疫系统杀死肿瘤的抗肿瘤药物。我们系统评价的主要目的是调查器官排斥的风险因素和 ICIs 在实体器官移植受者 (SOTRs) 中的疗效。

方法

我们搜索了四个数据库以查找截至 2021 年 1 月的相关文章。共有 61 篇文章，涉及 106 个 SOTR，符合筛选标准，并被纳入我们的系统评价。对收集到的数据进行统计描述，采用logistic回归分析危险因素。

结果

44 名患者 (41.5%) 在 ICI 后出现宿主抗移植物反应 (HVGR)。mTOR 抑制剂（ICI 前）（p  = 0.069，OR = 0.377，95% CI 0.132–1.078）和钙调磷酸酶抑制剂（ICI 后）（p  = 0.056，OR = 0.375，95%CI 0.137–1.025）可能有助于降低HVGR 的发生率。激素（前 ICI）（p  = 0.026，OR = 3.150，95%CI 1.150–8.628）和抗代谢物（前 ICI）（p  = 0.022，OR = 3.214，95%CI 1.185–8.720）可能会产生不利影响ICI 的有效性。只有 35.6% 的患者对 ICI 治疗反应良好且未发生 HVGR。

结论

我们的系统评价总结了 ICI 在 SOTR 中的使用，并评估了 ICI 的功效和诱发 HVGR 的风险因素。通过危险因素分析，我们发现mTOR抑制剂和钙调磷酸酶抑制剂可能有助于减少HVGR的发生；激素和抗代谢药物可能对 ICI 的疗效产生不利影响。此外，HVGR的发生与ICIs疗效之间存在矛盾关系。