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病例报告:他克莫司和英夫利昔单抗治疗失败的免疫检查点抑制剂相关结肠炎患者接受托法替布治疗后缓解

Case Report: A severe case of immunosuppressant-refractory immune checkpoint inhibitor-mediated colitis rescued by tofacitinib.

机构信息

Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands.

Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, Netherlands.

出版信息

Front Immunol. 2023 Jun 26;14:1212432. doi: 10.3389/fimmu.2023.1212432. eCollection 2023.

Abstract

Immune checkpoint inhibitor therapy for cancer treatment can give rise to a variety of adverse events. Here we report a male patient with metastatic melanoma who experienced life-threatening colitis and duodenitis following treatment with ipilimumab and nivolumab. The patient did not respond to the first three lines of immunosuppressive therapy (corticosteroids, infliximab, and vedolizumab), but recovered well after administration of tofacitinib, a JAK inhibitor. Cellular and transcriptional data on colon and duodenum biopsies shows significant inflammation in the tissue, characterized by a large number of CD8 T cells and high expression of PD-L1. While cellular numbers do decrease during three lines of immunosuppressive therapy, CD8 T cells remain relatively high in the epithelium, along with PD-L1 expression in the involved tissue and expression of colitis-associated genes, indicating an ongoing colitis at that moment. Despite all immunosuppressive treatments, the patient has an ongoing tumor response with no evidence of disease. Tofacitinib might be a good candidate to consider more often for ipilimumab/nivolumab-induced colitis.

摘要

免疫检查点抑制剂治疗癌症会引发各种不良反应。本文报道了一例转移性黑色素瘤男性患者,在接受伊匹单抗和纳武利尤单抗治疗后出现危及生命的结肠炎和十二指肠炎。该患者对前三线免疫抑制治疗(皮质类固醇、英夫利昔单抗和维多珠单抗)均无反应,但在使用 JAK 抑制剂托法替布后恢复良好。结肠和十二指肠活检的细胞和转录数据显示组织中有明显炎症,大量 CD8 T 细胞浸润,PD-L1 高表达。虽然在前三线免疫抑制治疗期间细胞数量有所减少,但 CD8 T 细胞在肠上皮中仍相对较高,受累组织中 PD-L1 表达以及结肠炎相关基因的表达,表明此时仍存在结肠炎。尽管接受了所有免疫抑制治疗,该患者的肿瘤仍持续缓解,无疾病证据。托法替布可能是一个更好的选择,可更频繁地用于治疗伊匹单抗/纳武利尤单抗引起的结肠炎。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91f2/10331137/3c3cef5361e4/fimmu-14-1212432-g001.jpg

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