Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF

Eur J Immunol. 2010 Jan;40(1):22-35. doi: 10.1002/eji.200939903.


CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSC) contribute to tumor immune evasion by restraining the activity of CD8+ T-cells. Two major MDSC subsets were recently shown to play an equal role in MDSC-induced immune dysfunctions: monocytic- and granulocytic-like. We isolated three fractions of MDSC, i.e. CD11b+/Gr-1high, CD11b+/Gr-1int, and CD11b+/Gr-1low populations that were characterized morphologically, phenotypically and functionally in different tumor models. In vitro assays showed that CD11b+/Gr-1int cell subset, mainly comprising monocytes and myeloid precursors, was always capable to suppress CD8+ T-cell activation, while CD11b+/Gr-1high cells, mostly granulocytes, exerted appreciable suppression only in some tumor models and when present in high numbers. The CD11b+/Gr-1int but not CD11b+/Gr-1high cells were also immunosuppressive in vivo following adoptive transfer. CD11b+/Gr-1low cells retained the immunosuppressive potential in most tumor models. Gene silencing experiments indicated that GM-CSF was necessary to induce preferential expansion of both CD11b+/Gr-1int and CD11b+/Gr-1low subsets in the spleen of tumor-bearing mice and mediate tumor-induced tolerance whereas G-CSF, which preferentially expanded CD11b+/Gr-1high cells, did not create such immunosuppressive environment. GM-CSF also acted on granulocyte-macrophage progenitors in the bone marrow inducing local expansion of CD11b+/Gr-1low cells. These data unveil a hierarchy of immunoregulatory activity among MDSC subsets that is controlled by tumor-released GM-CSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11b Antigen / immunology*
  • Cell Differentiation
  • Cell Line, Tumor
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Immune Tolerance*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Cells / cytology
  • Myeloid Cells / immunology*
  • Neoplasm Transplantation
  • Neoplasms / immunology
  • RNA Interference
  • Receptors, Chemokine / immunology*


  • CD11b Antigen
  • Gr-1 protein, mouse
  • Receptors, Chemokine
  • Granulocyte-Macrophage Colony-Stimulating Factor