title: A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells.
abstract: We recently demonstrated that human BM cells can be treated in vitro with defined growth factors to induce the rapid generation of myeloid-derived suppressor cells (MDSCs), hereafter defined as BM-MDSCs. Indeed, combination of G-CSF + GM-CSF led to the development of a heterogeneous mixture of immature myeloid cells ranging from myeloblasts to band cells that were able to suppress alloantigen- and mitogen-stimulated T lymphocytes. Here, we further investigate the mechanism of suppression and define the cell subset that is fully responsible for BM-MDSC-mediated immune suppression. This population, which displays the structure and markers of promyelocytes, is however distinct from physiologic promyelocytes that, instead, are devoid of immuosuppressive function. In addition, we demonstrate that promyelocyte-like cells proliferate in the presence of activated lymphocytes and that, when these cells exert suppressive activity, they do not differentiate but rather maintain their immature phenotype. Finally, we show that promyelocyte-like BM-MDSCs are equivalent to MDSCs present in the blood of patients with breast cancer and patients with colorectal cancer and that increased circulating levels of these immunosuppressive myeloid cells correlate with worse prognosis and radiographic progression.
authors: Department of Oncology and Surgical Sciences, Oncology Section, University of Padova, Padova, Italy.
authors: Samantha
authors: S
authors: Solito
authors: Erika
authors: E
authors: Falisi
authors: Claudia Marcela
authors: CM
authors: Diaz-Montero
authors: Andrea
authors: A
authors: Doni
authors: Laura
authors: L
authors: Pinton
authors: Antonio
authors: A
authors: Rosato
authors: Samuela
authors: S
authors: Francescato
authors: Giuseppe
authors: G
authors: Basso
authors: Paola
authors: P
authors: Zanovello
authors: Georgiana
authors: G
authors: Onicescu
authors: Elizabeth
authors: E
authors: Garrett-Mayer
authors: Alberto J
authors: AJ
authors: Montero
authors: Vincenzo
authors: V
authors: Bronte
authors: Susanna
authors: S
authors: Mandruzzato
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007945:Leukemia, Lymphoid / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D022423:Myeloid Cells / Q000145:classification / Q000276:immunology* / Q000473:pathology*; D038042:Myelopoiesis / Q000276:immunology; D011379:Prognosis; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C509295:ITGAM protein, human; D017452:Receptors, IgG