title: Myeloid derived suppressor cells (MDSCs) are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs) in chronic myeloid leukemia patients.
abstract: Tumor immune tolerance can derive from the recruitment of suppressor cell population, including myeloid derived suppressor cells (MDSCs), able to inhibit T cells activity. We identified a significantly expanded MDSCs population in chronic myeloid leukemia (CML) patients at diagnosis that decreased to normal levels after imatinib therapy. In addition, expression of arginase 1 (Arg1) that depletes microenvironment of arginine, an essential aminoacid for T cell function, resulted in an increase in patients at diagnosis. Purified CML CD11b+CD33+CD14-HLADR- cells markedly suppressed normal donor T cell proliferation in vitro. Comparing CML Gr-MDSCs to autologous polymorphonuclear leukocytes (PMNs) we observed a higher Arg1 expression and activity in PMNs, together with an inhibitory effect on T cells in vitro. Our data indicate that CML cells create an immuno-tolerant environment associated to MDSCs expansion with immunosuppressive capacity mediated by Arg1. In addition, we demonstrated for the first time also an immunosuppressive activity of CML PMNs, suggesting a strong potential immune escape mechanism created by CML cells, which control the anti-tumor reactive T cells. MDSCs should be monitored in imatinib discontinuation trials to understand their importance in relapsing patients.
authors.affiliation: Department of Clinical and Molecular Biomedicine, section of Hematology, Ferrarotto Hospital, University of Catania, Catania, Italy.
authors.forename: Cesarina
authors.initials: C
authors.lastname: Giallongo
authors.affiliation: Department of Clinical and Molecular Biomedicine, section of Hematology, Ferrarotto Hospital, University of Catania, Catania, Italy.
authors.forename: Nunziatina
authors.initials: N
authors.lastname: Parrinello
authors.affiliation: Department of Clinical and Molecular Biomedicine, section of Hematology, Ferrarotto Hospital, University of Catania, Catania, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Tibullo
authors.affiliation: Department of Clinical and Molecular Biomedicine, section of Hematology, Ferrarotto Hospital, University of Catania, Catania, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: La Cava
authors.affiliation: Department of Clinical and Molecular Biomedicine, section of Hematology, Ferrarotto Hospital, University of Catania, Catania, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romano
authors.affiliation: Department of Clinical and Molecular Biomedicine, section of Hematology, Ferrarotto Hospital, University of Catania, Catania, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiarenza
authors.affiliation: Department of Drug Sciences, section of Biochemistry, University of Catania, Catania, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Barbagallo
authors.affiliation: Department of Clinical and Molecular Biomedicine, section of Hematology, Ferrarotto Hospital, University of Catania, Catania, Italy.
authors.forename: Giuseppe A
authors.initials: GA
authors.lastname: Palumbo
authors.affiliation: Department of Clinical and Molecular Biomedicine, section of Hematology, Ferrarotto Hospital, University of Catania, Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.affiliation: Department of Pediatric and Medical Sciences, University of Catania, Catania, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vigneri
authors.affiliation: Department of Clinical and Molecular Biomedicine, section of Hematology, Ferrarotto Hospital, University of Catania, Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
mesh_terms: D000328:Adult; D000368:Aged; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D039481:CD11b Antigen / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018950:Lipopolysaccharide Receptors; D063268:Sialic Acid Binding Ig-like Lectin 3; C574619:ARG1 protein, human; D001119:Arginase