title: Mesenchymal Stem Cells (MSC) Regulate Activation of Granulocyte-Like Myeloid Derived Suppressor Cells (G-MDSC) in Chronic Myeloid Leukemia Patients.
abstract: It is well known that mesenchymal stem cells (MSC) have a role in promotion of tumor growth, survival and drug-resistance in chronic myeloid leukemia (CML). Recent reports indicated that a subpopulation of myeloid cells, defined as granulocyte-like myeloid-derived suppressor cells (G-MDSC) is increased in these patients. So far, the role of MSC in MDSC expansion and activation into the BM microenvironment remains unexplored. To address this question, here we use a specific experimental model in vitro, co-culturing MSC with peripheral blood mononucleated cells (PBMC) from normal individuals, in order to generate MSC-educated G-MDSC. Although MSC of healthy donors (HD) and CML patients were able to generate the same amount of MDSC, only CML-MSC-educated G-MDSC exhibited suppressive ability on autologous T lymphocytes. In addition, compared with HD-MSC, CML-MSC over-expressed some immunomodulatory factors including TGFβ, IL6 and IL10, that could be involved in MDSC activation. CML-MSC-educated G-MDSC expressed higher levels of ARG1, TNFα, IL1β, COX2 and IL6 than G-MDSC isolated from co-culture with HD-MSC. Our data provide evidence that CML-MSC may play a critical role in tumor microenvironment by orchestrating G-MDSC activation and regulating T lymphocytes-mediated leukemia surveillance, thus contributing to CML immune escape.
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Catania, Italy.|Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Cesarina
authors.initials: C
authors.lastname: Giallongo
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Catania, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romano
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Catania, Italy.
authors.forename: Nunziatina Laura
authors.initials: NL
authors.lastname: Parrinello
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Catania, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: La Cava
authors.affiliation: Department of Biological, Geological, and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Maria Violetta
authors.initials: MV
authors.lastname: Brundo
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bramanti
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.affiliation: Oncology, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vigneri
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Catania, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiarenza
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Catania, Italy.
authors.forename: Giuseppe Alberto
authors.initials: GA
authors.lastname: Palumbo
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Catania, Italy.|Department of Biological, Geological, and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Tibullo
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006098:Granulocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D009363:Neoplasm Proteins