We recently demonstrated that human bone marrow (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 morphology and markers of promyelocytes, is however distinct from physiological 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 breast and colorectal cancer patients and that increased circulating levels of these immunosuppressive myeloid cells correlate with worse prognosis and radiographic progression.

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

S. Solito;Bronte, Vincenzo;
2011-01-01

Abstract

We recently demonstrated that human bone marrow (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 morphology and markers of promyelocytes, is however distinct from physiological 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 breast and colorectal cancer patients and that increased circulating levels of these immunosuppressive myeloid cells correlate with worse prognosis and radiographic progression.
2011
myeloid differentiation; cancer; cytokine; T lymphocyte
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/359869
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