Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease.
Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease.
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DOI：
10.1038/s41598-021-88824-1
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发表时间：
2021-04-29
影响因子：
4.6
通讯作者：
Nishida N
中科院分区：
文献类型：
--
作者：
Hagiwara S;Watanabe T;Kudo M;Minaga K;Komeda Y;Kamata K;Kimura M;Hayashi H;Nakagawa K;Ueshima K;Minami Y;Aoki T;Takita M;Morita M;Cishina H;Ida H;Park AM;Nishida N
针对程序性细胞死亡1 （PD-1）和细胞毒性t淋巴细胞抗原-4 （CTLA-4）的免疫检查点抑制剂（ICIs）被广泛用于治疗晚期转移性癌症。ICIs中和PD-1或CTLA-4会导致免疫相关不良事件（irAEs）。我们评估了12例肝脏irae患者的临床病理特征，并与10例自身免疫性肝炎（AIH）或移植物抗宿主病（GVHD）患者的临床病理特征进行了比较。血清转氨酶水平无显著差异，而AIH患者血清IgG和抗核抗体水平高于GVHD或肝脏irae患者。GVHD或肝脏irAEs患者的炎症仅限于肝叶，而AIH患者则表现出门叶和小叶炎症。免疫组织化学分析显示，在肝脏irAEs和GVHD患者的小叶区，CD8+ T细胞的浸润和表达叉头盒p3 （FOXP3）的调节性T细胞（Tregs）的缺陷性积累。相比之下，AIH患者门静脉周围病变的特征是CD4+ T细胞、CD8+ T细胞、CD20+ B细胞和FOXP3+ Tregs细胞浸润。总之，在没有Tregs激活的情况下，CD8+ T细胞的激活可能是肝脏irAEs免疫发病机制的基础。
Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) are widely used to treat advanced metastatic cancers. Neutralisation of PD-1 or CTLA-4 by ICIs results in immune-related adverse events (irAEs). The clinicopathological features of twelve patients with hepatic irAEs were evaluated and compared to those of ten patients with autoimmune hepatitis (AIH) or graft-versus-host disease (GVHD). No significant difference was seen in serum levels of transaminases, whereas serum levels of IgG and anti-nuclear antibody were higher in patients with AIH than in those with GVHD or hepatic irAEs. Inflammation was limited to the liver lobes in patients with GVHD or hepatic irAEs, whereas patients with AIH exhibited both portal and lobular inflammation. Immunohistochemical analyses revealed a predominant infiltration of CD8+ T cells and defective accumulation of regulatory T cells (Tregs) expressing forkhead box p3 (FOXP3) in the lobular areas of patients with hepatic irAEs and GVHD. In contrast, periportal lesions of patients with AIH were characterised by an infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ Tregs. Overall, the activation of CD8+ T cells in the absence of activation of Tregs potentially underlies the immunopathogenesis of hepatic irAEs.
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DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
DOI：
10.1038/s41577-019-0218-4
发表时间：
2020-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Kalbasi A;Ribas A
通讯作者：
Ribas A
影响因子：
25.7
作者：
Peiseler, Moritz;Sebode, Marcial;Herkel, Johannes
通讯作者：
Herkel, Johannes
免疫检查点抑制剂与化疗治疗晚期非小细胞肺癌的对比分析：随机对照试验的荟萃分析
影响因子：
1.6
作者：
Khan M;Lin J;Liao G;Tian Y;Liang Y;Li R;Liu M;Yuan Y
通讯作者：
Yuan Y
影响因子：
20.3
作者：
Asano, Takeru;Meguri, Yusuke;Matsuoka, Ken-ichi
通讯作者：
Matsuoka, Ken-ichi