Expression and Prognostic Value of a Novel B7-H3 (CD276) Antibody in Acute Myeloid Leukemia

Author:

Stefańczyk Sylwia A.12ORCID,Hayn Clara12ORCID,Heitmann Jonas12,Jung Susanne123,Zekri Latifa12,Märklin Melanie12ORCID

Affiliation:

1. Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, 72076 Tuebingen, Germany

2. Cluster of Excellence iFIT (EXC 2180) ‘Image-Guided and Functionally Instructed Tumor Therapies’, Eberhard Karls University Tuebingen, 72076 Tuebingen, Germany

3. Department of Peptide−based Immunotherapy, Institute of Immunology, University and University Hospital Tuebingen, 72076 Tuebingen, Germany

Abstract

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-H3high and B7-H3low 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.

Funder

Deutsche Forschungsgemeinschaft DFG

Deutsche Krebshilfe

Open Access Publishing Fund of the University of Tuebingen

Publisher

MDPI AG

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