Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis.
Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis.
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DOI：
10.1080/2162402x.2016.1209615
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发表时间：
2016
期刊：
影响因子：
7.2
通讯作者：
Ottensmeier C
中科院分区：
文献类型：
--
作者：
Arriola E;Wheater M;Lopez MA;Thomas G;Ottensmeier C
大约30%的接受伊匹单抗治疗的患者会出现胃肠道毒性。支持人体组织临床观察的免疫驱动因素知之甚少。我们在此报告了易普利姆玛治疗对治疗相关性结肠炎患者结直肠粘膜的免疫影响。采用免疫组织化学方法，我们评估了20例易普利姆单抗相关性结肠炎患者结肠活检组织中CD 8+、FoxP 3和颗粒酶B（Gzm B）的免疫浸润。我们评估了10例正常结肠活检进行比较。在8例病例中（4例仅使用类固醇，4例使用类固醇和英夫利西单抗），我们评价了两次连续活检。我们观察到，与正常结肠相比，伊匹单抗相关性结肠炎患者的CD 8+、FoxP 3+和GzmB T细胞计数显著更高（p < 0.0001）。需要英夫利西单抗治疗结肠炎的患者的CD 8 +/FoxP 3比值显著高于仅接受类固醇治疗的患者，这与临床严重程度相关。重复样本的分析显示，在接受类固醇和英夫利西单抗治疗的患者中，结肠炎的消退与CD 8+和FoxP 3+细胞的减少相关。我们的数据表明，伊匹单抗相关性结肠炎患者结肠粘膜中细胞毒性T细胞和T淋巴细胞计数与临床结果相关，可预测严重程度并指导治疗。
Approximately 30% of patients treated with ipilimumab will develop gastrointestinal toxicity. The immunological drivers that underpin the clinical observations in human tissues are poorly understood. We report here on the immune consequences of ipilimumab treatment in the colorectal mucosa of patients with treatment-related colitis. Using immunohistochemistry, we evaluated the immune infiltrate by CD8+, FoxP3, and granzyme B (GzmB) in colonic biopsies from 20 patients with ipilimumab-related colitis. We assessed 10 cases with normal colon biopsies for comparison. In eight cases (four on steroids only, four on steroids and infliximab), we evaluated two sequential biopsies. We observed that CD8+, FoxP3+, and GzmB T cell counts were significantly higher in patients with ipilimumab-related colitis compared to normal colon (p < 0.0001). Patients who required infliximab for the resolution of their colitis had a significantly higher CD8+/FoxP3 ratio than those treated only with steroids and this correlated with clinical severity. The analysis of repeat samples revealed that resolution of the colitis was associated with a decrease in CD8+ and FoxP3+ cells both in patients treated with steroids and infliximab. Our data suggest that counts of cytotoxic T cells and Tregs in the colonic mucosa from patients with ipilimumab-related colitis correlate with clinical findings and may predict severity and guide management.