Biology and Microenvironment
A. Alonso1,*, B. Lopez-Pereira2,*, Corte1,*, S. Alonso-Alvarez3, I. Fernandez-Vega1, M. A. García-Moro4, T. Bernal3, R. Alonso-Arias4, E. Colado3
1Hospital Universitario Central de Asturias, Department of Pathology,2Hospital Alvarez-Buylla, Departament of Hematology,3Hospital Universitario Central de Asturias, Department of Hematology,4Hospital Universitario Central de Asturias, Department of Immunology
Introduction: CD47 over expression has been reported in several tumor subtypes. CD47 interacts with SIRP-alpha on macrophages inhibiting phagocytic signal, providing a survival advantage to tumor. CD47, therefore, represents a valuable target for immunotherapy and is currently under clinical investigation. We aimed to study CD47 expression in Hodgkin Reed Sternberg cells (HRS).
Material and Methods: We tested a polyclonal CD47 antibody (LifeSpan Biosciences, Seattle, WA) expression along with classical HRS cell markers on a tissue array of 13 classical Hodgkin Lymphoma (CHL) tumor biopsies obtained from newly diagnosed, non-selected patients (6 Female, 7 Male patients) in our institution from October 2016 to January 2018. Histologic subtypes were Nodular sclerosis in 8 cases, Mixed Cellularity in 3 cases and Lymphocyte rich in 2 additional cases. Median age was 52 years (Range: 8, 71) Early stage disease was found in 3 patients without unfavorable prognostic factors according to EORTC and GHSG criteria, one patient with unfavorable prognostic factors and 9 patients had advanced disease. Bulk disease was present in one patient. Normal lymphoid tissue and normal prostate epithelium were used as normal controls as recommended by manufacturer. Approval from the Local Ethical committee was obtained before any analysis.
Results: HRS cells were identified in formalin fixed paraffin embedded sections using CD30, which was overexpressed on all HRS cells with a characteristic dot-like pattern. HRS clearly expressed CD47, with both membrane and cytoplasmatic staining. HRS were stained more intensely than infiltrating normal T and stromal cells (Figure 1).
Discussion: We propose that HRS cells, by up-regulating CD47, might avoid innate immunity check on tumor growth. This represents a novel finding of an actionable target as CD47 overexpression could be circumvented using blocking monoclonal antibodies.