Stefańczyk Sylwia A, Hayn Clara, Heitmann Jonas, Jung Susanne, Zekri Latifa, Märklin Melanie
Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, 72076 Tuebingen, Germany.
Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', Eberhard Karls University Tuebingen, 72076 Tuebingen, Germany.
Cancers (Basel). 2024 Jul 4;16(13):2455. doi: 10.3390/cancers16132455.
Despite recent advances in immunophenotyping, the prognosis of acute myeloid leukemia (AML) is still mainly estimated using age and genetic markers. As the genetic heterogeneity of AML patients is high, flow cytometry-based classification with appropriate biomarkers can efficiently complement risk stratification and treatment selection. An increased expression of B7-H3 (CD276), an immune checkpoint protein, has been reported and associated with poor prognosis. However, the available data are limited and heterogeneous. Here, we used a novel, proprietary murine anti-B7-H3 8H8 antibody for the flow cytometric analysis of B7-H3 expression in AML blasts from 77 patients. Our antibody reliably detected substantial B7-H3 expression in 62.3% of AML patients. B7-H3 expression was higher in the monocytic French-American-British (FAB) M5 group and in intermediate and poor risk patients according to the European Leukemia Network. Using receiver operating characteristics (ROCs), we identified a specific fluorescence intensity cut-off of 4.45 to discriminate between B7-H3 and B7-H3 expression. High B7-H3 expression was associated with shorter overall survival (OS) and progression-free survival (PFS). In conclusion, we have developed a novel B7-H3 antibody that serves as a new tool for the detection of B7-H3 expression in AML and may help to facilitate risk stratification and treatment selection in AML patients.
尽管免疫表型分析最近取得了进展，但急性髓系白血病（AML）的预后仍主要通过年龄和基因标志物来评估。由于AML患者的基因异质性较高，基于流式细胞术并结合适当生物标志物的分类可以有效补充风险分层和治疗选择。据报道，免疫检查点蛋白B7-H3（CD276）表达增加且与预后不良相关。然而，现有数据有限且参差不齐。在此，我们使用一种新型的、专有的鼠抗B7-H3 8H8抗体，对77例患者的AML原始细胞中B7-H3的表达进行流式细胞术分析。我们的抗体在62.3%的AML患者中可靠地检测到了显著的B7-H3表达。根据欧洲白血病网络，B7-H3在单核细胞型法美英（FAB）M5组以及中危和高危患者中表达更高。利用受试者工作特征曲线（ROC），我们确定了一个4.45的特定荧光强度临界值，以区分B7-H3阳性和阴性表达。高B7-H3表达与总生存期（OS）和无进展生存期（PFS）缩短相关。总之，我们开发了一种新型B7-H3抗体，它可作为检测AML中B7-H3表达的新工具，并可能有助于促进AML患者的风险分层和治疗选择。
