title: Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients.
abstract: Human granulocytic myeloid-derived suppressor cells (G-MDSCs) have been described as low-density immunosuppressive CD66b+CD33dimHLA-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+CD33dimHLA-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+CD33dimHLA-DR-cells and patient clinicopathological features and outcome, were evaluated.CD66b+CD33dimHLA-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+CD33dimHLA-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+CD33dimHLA-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+CD33dimHLA-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.
authors.affiliation: Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.|Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
authors.forename: Olivia
authors.initials: O
authors.lastname: Marini
authors.affiliation: Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Spina
authors.affiliation: Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.
authors.forename: Elda
authors.initials: E
authors.lastname: Mimiola
authors.affiliation: Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cassaro
authors.affiliation: Department of Neurological, Biomedical and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malerba
authors.affiliation: Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Todeschini
authors.affiliation: Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.
authors.forename: Omar
authors.initials: O
authors.lastname: Perbellini
authors.affiliation: Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.|Department of Inderdepartmental Laboratory for Medical Research (LURM), University of Verona, Verona, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Scupoli
authors.affiliation: Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carli
authors.affiliation: Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Facchinelli
authors.affiliation: Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cassatella
authors.affiliation: Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Scapini
authors.affiliation: Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tecchio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D006098:Granulocytes / Q000276:immunology* / Q000473:pathology; D006689:Hodgkin Disease / Q000097:blood* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D055815:Young Adult
keywords: Hodgkin lymphoma; granulocytic myeloid-derived suppressor cells; low-density neutrophils; non-Hodgkin lymphoma; normal-density neutrophils