B López-Pereira1, A A Fernández-Velasco2, I Fernández-Vega2, D Corte-Torres2, C Quirós3,4, J A Villegas5, P Palomo3, S González3, A P González3, Á Payer3, T Bernal3, M A Moro-García4, R Alonso-Arias4,6, S Alonso-Álvarez3,4, E Colado7,8. 1. Department of Hematology, Alvarez Buylla Hospital, Mieres, Asturias, Spain. 2. Department of Pathology, University Hospital Central de Asturias, Oviedo, Asturias, Spain. 3. Department of Hematology, University Hospital Central de Asturias, Oviedo, Asturias, Spain. 4. Department of Laboratory Medicine, University Hospital Central de Asturias, Oviedo, Asturias, Spain. 5. Department of Pediatrics, University Hospital Central de Asturias, Oviedo, Asturias, Spain. 6. Department of Immunology, University Hospital Central de Asturias, Oviedo, Asturias, Spain. 7. Department of Hematology, University Hospital Central de Asturias, Oviedo, Asturias, Spain. enrique.colado@sespa.es. 8. Department of Laboratory Medicine, University Hospital Central de Asturias, Oviedo, Asturias, Spain. enrique.colado@sespa.es.
Abstract
INTRODUCTION: CD47 over expression has been reported in several tumor subtypes. CD47 interacts with SIRPalpha 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). METHODS: We tested a polyclonal CD47 antibody (LifeSpan Biosciences, Seattle, WA) expression along with classical HRS cell markers on a tissue array of 16 classical Hodgkin Lymphoma (CHL) tumor biopsies obtained from newly diagnosed, non-selected patients (8 Female, 8 Male patients) in our institution from October 2016 to January 2018. Histologic subtypes were nodular sclerosis in 11 cases, mixed Cellularity in 3 cases and lymphocyte rich in 2 additional cases. Median age was 53 years (Range: 8, 74). Early stage disease was found in three patients without unfavorable prognostic factors according to EORTC and GHSG criteria, one patient with unfavorable prognostic factors and nine 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: CD47 was overexpressed on all HRS cells with a characteristic dot-like pattern in 13/13 cases of CHL. HRS clearly expressed CD47 more intensely than infiltrating T and stromal cells. DISCUSSION: We propose that HRS cells, by up-regulating CD47, might avoid innate immunity check on tumor growth, which could be circumvented using blocking monoclonal antibodies.
INTRODUCTION:CD47 over expression has been reported in several tumor subtypes. CD47 interacts with SIRPalpha 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). METHODS: We tested a polyclonal CD47 antibody (LifeSpan Biosciences, Seattle, WA) expression along with classical HRS cell markers on a tissue array of 16 classical Hodgkin Lymphoma (CHL) tumor biopsies obtained from newly diagnosed, non-selected patients (8 Female, 8 Male patients) in our institution from October 2016 to January 2018. Histologic subtypes were nodular sclerosis in 11 cases, mixed Cellularity in 3 cases and lymphocyte rich in 2 additional cases. Median age was 53 years (Range: 8, 74). Early stage disease was found in three patients without unfavorable prognostic factors according to EORTC and GHSG criteria, one patient with unfavorable prognostic factors and nine 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:CD47 was overexpressed on all HRS cells with a characteristic dot-like pattern in 13/13 cases of CHL. HRS clearly expressed CD47 more intensely than infiltrating T and stromal cells. DISCUSSION: We propose that HRS cells, by up-regulating CD47, might avoid innate immunity check on tumor growth, which could be circumvented using blocking monoclonal antibodies.
Entities:
Keywords:
Cluster of differentiation 47; Hodgkin lymphoma; Microenvironment; Tumor evasion
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