A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells

Samantha Solito, Erika Falisi, Claudia Marcela Diaz-Montero, Andrea Doni, Laura Pinton, Antonio Rosato, Samuela Francescato, Giuseppe Basso, Paola Zanovello, Georgiana Onicescu, Elizabeth Garrett-Mayer, Alberto J. Montero, Vincenzo Bronte, Susanna Mandruzzato

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2254-2265
Number of pages12
JournalBlood
Volume118
Issue number8
DOIs
Publication statusPublished - Aug 25 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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  • Cite this

    Solito, S., Falisi, E., Diaz-Montero, C. M., Doni, A., Pinton, L., Rosato, A., Francescato, S., Basso, G., Zanovello, P., Onicescu, G., Garrett-Mayer, E., Montero, A. J., Bronte, V., & Mandruzzato, S. (2011). A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells. Blood, 118(8), 2254-2265. https://doi.org/10.1182/blood-2010-12-325753