Distinct Immunophenotypes of T Cells in Bronchoalveolar Lavage Fluid From Leukemia Patients With Immune Checkpoint Inhibitors-Related Pulmonary Complications.
Distinct Immunophenotypes of T Cells in Bronchoalveolar Lavage Fluid From Leukemia Patients With Immune Checkpoint Inhibitors-Related Pulmonary Complications.
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来自与免疫检查点抑制剂相关肺并发症的白血病患者的支气管肺泡灌洗液中T细胞的独特免疫表型。
DOI：
10.3389/fimmu.2020.590494
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发表时间：
2020
影响因子：
7.3
通讯作者：
Daver N
中科院分区：
文献类型：
--
作者：
Kim ST;Sheshadri A;Shannon V;Kontoyiannis DP;Kantarjian H;Garcia-Manero G;Ravandi F;Im JS;Boddu P;Bashoura L;Balachandran DD;Evans SE;Faiz S;Ruiz Vazquez W;Divenko M;Mathur R;Tippen SP;Gumbs C;Neelapu SS;Naing A;Wang L;Diab A;Futreal A;Nurieva R;Daver N
接受免疫检查点抑制剂（ICI）治疗的急性髓性白血病（AML）和骨髓增生异常综合征（MDS）患者有发生肺炎和肺炎（以下合并为ICI相关肺部并发症）的风险。关于ICI相关肺部并发症的细胞和分子机制知之甚少。我们对来自7例经ICI治疗后出现肺部症状的AML/MDS患者（ICI组）和4例伴有细胞外细菌性或真菌性肺炎的ICI初治AML/MDS患者（对照组）的支气管肺泡灌洗液（BAL）和外周血中的淋巴细胞进行了表征。ICI组中的BAL T细胞克隆扩增，ICI组中的BAL IFNγ+ IL-17− CD 8 + T和CXCR 3 + CCR 6 + Th 17/Th 1细胞富集。我们的数据表明，这些细胞可能在ICI相关肺部并发症的病理生理学中发挥关键作用。了解这些细胞群也可以提供ICI相关肺部并发症的预测和诊断生物标志物，最终使接受ICI治疗的AML/MDS患者能够区分肺炎。
Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) treated with immune checkpoint inhibitors (ICIs) are at risk of pneumonitis as well as pneumonia (combined henceforth as ICI-related pulmonary complications). Little is known about the cellular and molecular mechanisms underlying ICI-related pulmonary complications. We characterized lymphocytes from bronchoalveolar lavage (BAL) fluid and peripheral blood from seven AML/MDS patients with pulmonary symptoms after ICI-based therapy (ICI group) and four ICI-naïve AML/MDS patients with extracellular bacterial or fungal pneumonias (controls). BAL T cells in the ICI group were clonally expanded, and BAL IFNγ+ IL-17− CD8+ T and CXCR3+ CCR6+ Th17/Th1 cells were enriched in the ICI group. Our data suggest that these cells may play a critical role in the pathophysiology of ICI-related pulmonary complications. Understanding of these cell populations may also provide predictive and diagnostic biomarkers of ICI-related pulmonary complications, eventually enabling differentiation of pneumonitis from pneumonia in AML/MDS patients receiving ICI-based therapies.