Mechanisms of immune checkpoint inhibitor-mediated liver injury.
Mechanisms of immune checkpoint inhibitor-mediated liver injury.
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DOI：
10.1016/j.apsb.2021.10.003
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Dara L
中科院分区：
文献类型：
--
作者：
Shojaie L;Ali M;Iorga A;Dara L
免疫检查点，细胞毒性T淋巴细胞相关抗原4（CTLA-4）和程序性细胞死亡蛋白-1/配体-1（PD-1/PD-L1）是免疫调节和耐受的重要因素。最近，免疫检查点抑制剂（ICI）已经彻底改变了癌症治疗;然而，它们伴随着涉及多个器官（如肝脏）的免疫相关不良事件的代价。由于其持续暴露于外源抗原，肝脏已经进化出高免疫耐受能力，因此，免疫检查点的阻断可能导致高达20%的患者的异常免疫激活，这取决于所使用的药物和潜在因素。这种类型的肝毒性被称为检查点抑制剂（ILICI）引起的免疫介导的肝损伤，当CTLA 4和PD-1/PD-L1联合使用时更常见。这种独特类型的肝毒性的潜在机制尚未完全了解;然而，CD 8+细胞毒性T淋巴细胞、各种CD 4 + T细胞群、细胞因子和先天免疫系统的二次激活导致肝损伤的作用均已提出。本文综述了我们目前对ILICI动物模型免疫治疗中肝损伤机制的认识以及临床研究中的患者数据。免疫检查点抑制剂引起肝损伤的潜在机制尚不清楚。针对CTLA-4和PD-1/PD-L1的抗体激活细胞毒性T淋巴细胞以攻击癌细胞。其非预期后果是免疫相关的不良反应，如肝毒性。目前尚不清楚肝损伤的发生是由于T细胞的直接毒性还是由于马槟榔碱介导的先天免疫细胞激活。
The immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein-1/ligand-1 (PD-1/PD-L1) are vital contributors to immune regulation and tolerance. Recently immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy; however, they come with the cost of immune related adverse events involving multiple organs such as the liver. Due to its constant exposure to foreign antigens, the liver has evolved a high capacity for immune tolerance, therefore, blockade of the immune checkpoints can result in aberrant immune activation affecting the liver in up to 20% of patients depending on the agent(s) used and underlying factors. This type of hepatotoxicity is termed immune mediated liver injury from checkpoint inhibitors (ILICI) and is more common when CTLA4 and PD-1/PD-L1 are used in combination. The underlying mechanisms of this unique type of hepatotoxicity are not fully understood; however, the contribution of CD8+ cytotoxic T lymphocytes, various CD4+ T cells populations, cytokines, and the secondary activation of the innate immune system leading to liver injury have all been suggested. This review summarizes our current understanding of the underlying mechanisms of liver injury in immunotherapy using animal models of ILICI and available patient data from clinical studies. The underlying mechanism of liver injury from immune check point inhibitors is not known. Antibodies against CTLA-4 and PD-1/PD-L1 activate cytotoxic T lymphocytes to attack cancer cells. An unintended consequence of this is immune related adverse effects such as hepatotoxicity. It is unclear whether liver injury occurs due to direct toxicity from T cells or as a result of cytokine-mediated innate immune cell activation.
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影响因子：
1.5
作者：
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通讯作者：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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发表时间：
2009-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
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作者：
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