Journal Article

Mesenchymal Stem Cells (MSC) Regulate Activation of Granulocyte-Like Myeloid Derived Suppressor Cells (G-MDSC) in Chronic Myeloid Leukemia Patients

La Cava, Piera, Chiarenza, Annalisa, Brundo, Maria Violetta, Tibullo, Daniele, Bramanti, Vincenzo, Vigneri, Paolo, Giallongo, Cesarina, Di Raimondo, Francesco, Romano, Alessandra, Parrinello, Nunziatina Laura, Palumbo, Giuseppe Alberto, Stagno, Fabio

2016

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Autografts / Biology and Life Sciences / Cell activation / Cell culture / Cell survival / Chronic myeloid leukemia / Cloning / Cyclooxygenase-2 / Drug resistance / Education / Environmental science / Female / Granulocytes / Granulocytes - metabolism / Granulocytes - pathology / Hematology / Humans / Immune system / Immunology / Immunomodulation / Immunosuppressive agents / Interleukin 1 / Interleukin 10 / Interleukin 6 / Leukemia / Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism / Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology / Leukocytes (granulocytic) / Lymphocytes / Lymphocytes T / Male / Medical prognosis / Medical research / Medicine and Health Sciences / Mesenchymal stem cells / Mesenchymal Stromal Cells - metabolism / Mesenchymal Stromal Cells - pathology / Mesenchyme / Middle Aged / Models, Biological / Myeloid cells / Myeloid leukemia / Neoplasm Proteins - metabolism / Oncology / Patients / Peripheral blood mononuclear cells / Research and Analysis Methods / Stem cells / Suppressor cells / Tumor Microenvironment / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Tumors