Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients
| Autor: | Patrizia Scapini, Marco A. Cassatella, Olivia Marini, Davide Facchinelli, Cristina Tecchio, Cristina Spina, Giuseppe Carli, Maria Teresa Scupoli, Adriana Cassaro, Omar Perbellini, Elda Mimiola, Giovanni Malerba, Giuseppe Todeschini |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Adolescent CD33 Population MDSC lymphoma neutrophils Peripheral blood mononuclear cell Young Adult 03 medical and health sciences 0302 clinical medicine Immunophenotyping Internal medicine normal-density neutrophils medicine Humans Myeloid Cells education Hodgkin lymphoma granulocytic myeloid-derived suppressor cells low-density neutrophils non-Hodgkin lymphoma Aged Cell Proliferation education.field_of_study Hematology business.industry Lymphoma Non-Hodgkin Myeloid-Derived Suppressor Cells Cancer Middle Aged medicine.disease Hodgkin Disease Lymphoma 030104 developmental biology Oncology 030220 oncology & carcinogenesis Immunology Myeloid-derived Suppressor Cell Female business Granulocytes Research Paper |
| Zdroj: | Oncotarget |
| Popis: | // Olivia Marini 1, 2 , Cecilia Spina 1 , Elda Mimiola 1 , Adriana Cassaro 1 , Giovanni Malerba 3 , Giuseppe Todeschini 1 , Omar Perbellini 1 , Maria Scupoli 1, 4 , Giuseppe Carli 1 , Davide Facchinelli 1 , Marco Cassatella 2 , Patrizia Scapini 2 , Cristina Tecchio 1 1 Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy 2 Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy 3 Department of Neurological, Biomedical and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy 4 Department of Inderdepartmental Laboratory for Medical Research (LURM), University of Verona, Verona, Italy Correspondence to: Cristina Tecchio, email: cristina.tecchio@univr.it Keywords: granulocytic myeloid-derived suppressor cells, Hodgkin lymphoma, non-Hodgkin lymphoma, low-density neutrophils, normal-density neutrophils Received: January 09, 2016 Accepted: March 18, 2016 Published: March 30, 2016 ABSTRACT Human granulocytic myeloid-derived suppressor cells (G-MDSCs) have been described as low-density immunosuppressive CD66b + CD33 dim HLA-DR-granulocytes that co-purify with mononuclear cells after density gradient centrifugation of blood from cancer patients. The role of G-MDSCs in Hodgkin (HL) and non-Hodgkin lymphoma (NHL) remains unclear. The percentage and immunophenotype of CD66b + CD33 dim HLA-DR-cells were analyzed in PBMCs from HL and B-cell NHL patients ( n = 124) and healthy donors ( n = 48). The immunosuppressive functions of these cells were tested in vitro . Correlations between CD66b + CD33 dim HLA-DR-cells and patient clinicopathological features and outcome, were evaluated. CD66b + CD33 dim HLA-DR-cells were increased in PBMCs from HL and B-cell NHL patients as compared to healthy donors: 2.18 (0.02–70.92) vs 0.42 (0.04–2.97), p < 0.0001. Their percentage remained significantly higher even considering HL ( n = 31), indolent ( n = 31) and aggressive ( n = 62) B-cell NHL patients separately: 1.54 (0.28–26.34), 2.15 (0.02–20.08), and 2.96 (0.25–70.92), respectively, p < 0.0001. CD66b + CD33 dim HLA-DR-cells in patient PBMCs were mostly composed of mature CD11b + CD16 + low-density neutrophils in an activated status, as revealed by their higher CD11b and CD66b expression as compared to conventionally isolated (normal-density) autologous or healthy donor neutrophils. The in vitro depletion of CD66b + cells from patient PBMCs restored the proliferation of autologous T cells. Higher frequencies of CD66b + CD33 dim HLA-DR – G-MDSCs correlated significantly with unfavorable prognostic index scores and a shorter freedom from disease progression. PBMCs from HL and B-cell NHL patients contain a population of CD66b + CD33 dim HLA-DR – G-MDSCs, mostly composed of activated low-density neutrophils with immunosuppressive properties. These findings disclose a previously unknown G-MDSC-mediated mechanism of immune-escape in lymphomas, therefore anticipating possible targets for therapeutic interventions. |
| Databáze: | OpenAIRE |
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