T follicular helper cells: linking cancer immunotherapy and immune-related adverse events.
T follicular helper cells: linking cancer immunotherapy and immune-related adverse events.
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DOI：
10.1136/jitc-2021-002588
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发表时间：
2021-06
影响因子：
10.9
通讯作者：
Brossart P
中科院分区：
文献类型：
--
作者：
Baumjohann D;Brossart P
利用免疫检查点抑制剂（ICI）的癌症免疫疗法已经彻底改变了许多癌症类型的治疗。由于这些治疗的潜在机制在于干扰通常损害强效抗肿瘤免疫的抑制信号，例如细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和程序性细胞死亡蛋白1（PD-1）：程序性死亡配体1/2（PD-L1/2）途径，因此这也可能促进对无关抗原特异性的过度适应性免疫应答并不奇怪。在临床上越来越多地观察到的基于ICI的癌症免疫疗法的副作用之一是免疫相关不良事件（irAE），包括各种类型的自身免疫。然而，确切的病因是不完全理解。T滤泡辅助细胞（Tfh）为B细胞提供了有效的抗体应答的必要帮助，并且它们的肿瘤组织存在通常与几种实体瘤实体的更好结果相关。重要的是，这些CD 4 + T细胞表达非常大量的PD-1和其他共刺激和抑制受体。在这里，我们提出了一个假设，即靶向CTLA-4或PD-1及其配体PD-L1对接受这些ICI的患者中Tfh细胞的功能产生了关键影响，从而提供了ICI治疗与继发性自身免疫发展之间的联系。
Cancer immunotherapy utilizing immune checkpoint inhibitors (ICIs) has revolutionized the treatment of numerous cancer types. As the underlying mechanism of these treatments lies in the interference with inhibitory signals that usually impair potent antitumor immunity, for example, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein 1 (PD-1):programmed death-ligand 1/2 (PD-L1/2) pathway, it is not surprising that this could also promote exaggerated adaptive immune responses to unrelated antigen specificities. One of the side effects of ICI-based cancer immunotherapy that is increasingly observed in the clinic is immune-related adverse events (irAEs), including various types of autoimmunity. However, the precise etiology is incompletely understood. T follicular helper (Tfh) cells provide essential help to B cells for potent antibody responses and their tumor tissue presence is often correlated with a better outcome in several solid tumor entities. Importantly, these CD4+ T cells express very high amounts of PD-1 and other co-stimulatory and inhibitory receptors. Here, we address the hypothesis that targeting CTLA-4 or PD-1 and its ligand PD-L1 critically impacts the function of Tfh cells in patients that receive these ICIs, thereby providing a link between ICI treatment and the development of secondary autoimmunity.
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