Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
Clin J Gastroenterol. 2021 Aug;14(4):1191-1196. doi: 10.1007/s12328-020-01317-y. Epub 2021 Mar 5.
Systemic administration of anti-programmed cell death 1 (PD-1) antibody (Ab) has achieved remarkable success in metastatic cancers. The blockade of PD-1-mediated signaling pathways sometimes cause immune-related adverse events (irAEs) due to restored anti-cancer as well as anti-self immunity. Although the liver is a preferential organ for irAEs, the immuno-pathogenesis underlying hepatic irAEs has been poorly understood. We describe a 57-year-old man with Stage IV lung cancer who underwent the first-line regimen composed of carboplatin and paclitaxel. Nivolumab treatment (3.2 mg/kg, every 3 weeks) was initiated when the disease progressed after the first chemotherapy. Sequential occurrence of irAEs involving the multiorgan systems was observed. He developed hepatic irAEs (Grade 3) after endocrine, lung, and cutaneous irAEs. Lobular hepatitis characterized by predominant infiltration of CD8 T cells was seen in the liver biopsy specimens. Interestingly, defective accumulation of regulatory T cells (Tregs) expressing forkhead box protein P3 (FOXP3) was evident in this case with hepatic irAEs as compared with typical cases with autoimmune hepatitis. This case suggests that hepatic irAEs are characterized not only by lobular infiltration of CD8 T cells but also by defective accumulation of FOXP3 Tregs.
抗程序性细胞死亡 1（PD-1）抗体（Ab）的系统给药在转移性癌症中取得了显著成功。由于恢复了抗癌和抗自身免疫，阻断 PD-1 介导的信号通路有时会引起免疫相关的不良反应（irAEs）。尽管肝脏是 irAEs 的首选器官，但肝 irAEs 的免疫发病机制仍知之甚少。我们描述了一名 57 岁的男性，患有 IV 期肺癌，接受了卡铂和紫杉醇的一线治疗方案。在第一次化疗后疾病进展时，开始使用nivolumab（3.2mg/kg，每 3 周一次）治疗。在发生内分泌、肺部和皮肤 irAEs 后，他出现了多器官系统的 irAEs。在肝活检标本中观察到以 CD8 T 细胞为主浸润的小叶性肝炎，表现为肝 irAEs（Grade 3）。有趣的是，与自身免疫性肝炎的典型病例相比，在发生肝 irAEs 的情况下，表达叉头框蛋白 P3（FOXP3）的调节性 T 细胞（Tregs）的缺陷积聚更为明显。该病例表明，肝 irAEs 的特征不仅是小叶性 CD8 T 细胞浸润，还包括 FOXP3 Tregs 的缺陷积聚。
