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Immune checkpoint inhibitor treatment induces colitis with heavy infiltration of CD8 + T cells and an infiltration pattern that resembles ulcerative colitis
Virchows Archiv ( IF 3.5 ) Pub Date : 2021-08-02 , DOI: 10.1007/s00428-021-03170-x
Sara Hone Lopez 1 , Gursah Kats-Ugurlu 2 , Remco J Renken 3, 4 , Henk J Buikema 2 , Marco R de Groot 5 , Marijn C Visschedijk 6 , Gerard Dijkstra 6 , Mathilde Jalving 1 , Jacco J de Haan 1
Affiliation  

Colitis is a common, but poorly understood, adverse event of immune checkpoint inhibitors that are standard-of-care for an expanding range of cancer types. This explorative study aimed to describe the immune infiltrates in the colon from individuals developing checkpoint inhibitor colitis and compare them to well-known immunophenotypes of acute graft-versus-host disease, ulcerative colitis, and Crohn’s disease. Colon biopsies (n = 20 per group) of patients with checkpoint inhibitor colitis, acute graft-versus-host disease, ulcerative colitis and Crohn’s disease, all colitis treatment-naïve, and of individuals with a normal colon were analyzed using immunohistochemistry: CD8 for cytotoxic T cells, CD4 for T helper cells, and CD68 to identify cells of macrophage lineage. CD8 + T cell, CD4 + T cell, and CD68 + cell counts were performed. Cell infiltration was scored as scattered/patchy or band-like in the superficial and deep gut mucosa. Checkpoint inhibitor colitis was found to be heavily infiltrated by CD8 + T cells. Comparative analysis between groups showed that both CD8 + T cell counts (P < 0.01) and immune cell infiltration patterns in checkpoint inhibitor colitis were most similar to those observed in ulcerative colitis, with a deep band-like CD4 + T cell infiltration pattern and a superficial band-like CD68 + cell infiltration pattern in both. In conclusion, this is the first immunohistopathological study comparing infiltrate characteristics of checkpoint inhibitor colitis, acute graft-versus-host disease, ulcerative colitis, and Crohn’s disease. Checkpoint inhibitor colitis samples are heterogeneous, heavily infiltrated by CD8 + T cells, and show an immune cell infiltration pattern that is more similar to ulcerative colitis than to colonic acute graft-versus-host disease or colonic Crohn’s disease.



中文翻译:

免疫检查点抑制剂治疗诱发结肠炎,CD8 + T 细胞大量浸润,浸润模式类似于溃疡性结肠炎

结肠炎是免疫检查点抑制剂的常见但知之甚少的不良事件,是越来越多癌症类型的标准治疗。这项探索性研究旨在描述发生检查点抑制剂结肠炎的个体在结肠中的免疫浸润,并将其与众所周知的急性移植物抗宿主病、溃疡性结肠炎和克罗恩病的免疫表型进行比较。结肠活检(n = 20 每组)检查点抑制剂结肠炎、急性移植物抗宿主病、溃疡性结肠炎和克罗恩病、所有结肠炎治疗初治和结肠正常的患者使用免疫组织化学进行分析:CD8 用于细胞毒性 T 细胞, CD4 用于 T 辅助细胞,CD68 用于识别巨噬细胞谱系的细胞。进行了 CD8 + T 细胞、CD4 + T 细胞和 CD68 + 细胞计数。细胞浸润在浅表和深部肠粘膜中被评分为分散/斑片状或带状。发现检查点抑制剂结肠炎被 CD8 + T 细胞大量浸润。组间比较分析表明,CD8 + T 细胞计数(P < 0.01) 和检查点抑制剂结肠炎中的免疫细胞浸润模式与溃疡性结肠炎中观察到的最相似,两者均具有深带状 CD4 + T 细胞浸润模式和浅表带状 CD68 + 细胞浸润模式。总之,这是第一项比较检查点抑制剂结肠炎、急性移植物抗宿主病、溃疡性结肠炎和克罗恩病的浸润特征的免疫组织病理学研究。检查点抑制剂结肠炎样本是异质的,被 CD8 + T 细胞大量浸润,并显示出与溃疡性结肠炎更相似的免疫细胞浸润模式,而不是结肠急性移植物抗宿主病或结肠克罗恩病。

更新日期:2021-08-03
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