Immune profiles in acute myeloid leukemia bone marrow associate with patient age, T-cell receptor clonality, and survival
Immune profiles in acute myeloid leukemia bone marrow associate with patient age, T-cell receptor clonality, and survival
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DOI：
10.1182/bloodadvances.2019000792
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发表时间：
2020-01-28
期刊：
影响因子：
7.5
通讯作者：
Mustjoki, Satu
中科院分区：
文献类型：
--
作者：
Bruck, Oscar;Dufva, Olli;Mustjoki, Satu
各种实体瘤中的免疫微环境是异常的，并且与临床存活相关。在这里，我们提出了一个全面的分析免疫环境的急性髓细胞白血病（AML）的骨髓（BM）在诊断。我们使用多重免疫组织化学和计算机图像分析技术，比较了急性髓细胞白血病（AML）（n = 69）、慢性髓细胞白血病（CML; n = 56）和B细胞急性淋巴细胞白血病（B-ALL）患者（n = 5 - 52）与对照组（n = 12）福尔马林固定石蜡包埋BM环钻样本的免疫学特征。我们确定了白血病亚型和对照组特异性的不同免疫学特征，能够准确分类AML（曲线下面积[AUC] = 1.0）、CML（AUC = 0.99）、B-ALL（AUC = 0.96）和对照组受试者（AUC = 1.0）。有趣的是，发现了2个在年龄、T细胞受体克隆性和存活率方面不同的主要免疫学AML簇。低比例的调节性T细胞和pSTAT（+）cMAF（-）单核细胞被确定为强化治疗AML患者中上级无事件生存期的新生物标志物。此外，我们证明了AML BM和外周血样品在免疫细胞表型方面是不同的。总之，我们的研究表明，白血病亚型的免疫景观有很大差异，这表明疾病特异性免疫调节。此外，AML免疫微环境与临床参数的相关性表明了纳入免疫学参数以改善疾病分类甚至患者风险分层的基本原理。
The immunologic microenvironment in various solid tumors is aberrant and correlates with clinical survival. Here, we present a comprehensive analysis of the immune environment of acute myeloid leukemia (AML) bone marrow (BM) at diagnosis. We compared the immunologic landscape of formalin-fixed paraffin-embedded BM trephine samples from AML (n = 69), chronic myeloid leukemia (CML; n = 56), and B-cell acute lymphoblastic leukemia (B-ALL) patients (n 5 52) at diagnosis to controls (n = 12) with 30 immunophenotype markers using multiplex immunohistochemistry and computerized image analysis. We identified distinct immunologic profiles specific for leukemia subtypes and controls enabling accurate classification of AML (area under the curve [AUC] = 1.0), CML (AUC = 0.99), B-ALL (AUC = 0.96), and control subjects (AUC = 1.0). Interestingly, 2 major immunologic AML clusters differing in age, T-cell receptor clonality, and survival were discovered. A low proportion of regulatory T cells and pSTAT(+)cMAF(-) monocytes were identified as novel biomarkers of superior event-free survival in intensively treated AML patients. Moreover, we demonstrated that AML BM and peripheral blood samples are dissimilar in terms of immune cell phenotypes. To conclude, our study shows that the immunologic landscape considerably varies by leukemia subtype suggesting disease-specific immunoregulation. Furthermore, the association of the AML immune microenvironment with clinical parameters suggests a rationale for including immunologic parameters to improve disease classification or even patient risk stratification.