Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4⁺ T cells from patients with GI malignancy

Cancer Immunol Immunother. 2011 Sep;60(9):1269-79. doi: 10.1007/s00262-011-1029-z. Epub 2011 May 21.


Interferon-alpha (IFN-α) promotes anti-tumor immunity through its actions on immune cells. We hypothesized that elevated percentages of myeloid-derived suppressor cells (MDSC) and increased pro-inflammatory cytokines in peripheral blood would be associated with impaired response to IFN-α in patients with gastrointestinal (GI) malignancies. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets, and IFN-α-induced signal transduction in 40 patients with GI malignancies. Plasma IL-6 and IL-10 were significantly higher in patients versus normal donors. CD33(+)HLADR(-)CD11b(+)CD15(+) and CD33(+)HLADR(-/low)CD14(+) MDSC subsets were also elevated in patients versus normal donors (P < 0.0001). Plasma IL-6 was correlated with CD33(+)HLADR(-)CD15(+) MDSC (P = 0.008) and IL-10 with CD33(+)HLADR(-)CD15(-) MDSC (P = 0.002). The percentage of CD15(+) and CD15(-) but not CD14(+) MDSC subsets were inversely correlated with IFN-α-induced STAT1 phosphorylation in CD4(+) T cells, while co-culture with in vitro generated MDSC led to reduced IFN-α responsiveness in both PBMC and the CD4(+) subset of T cells from normal donors. Exploratory multivariable Cox proportional hazards models revealed that an increased percentage of the CD33(+)HLADR(-)CD15(-) MDSC subset was associated with reduced overall survival (P = 0.049), while an increased percentage of the CD33(+)HLADR(-/low)CD14(+) subset was associated with greater overall survival (P = 0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets, and IFN-α responsiveness in patients with GI malignancies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Gastrointestinal Neoplasms / blood
  • Gastrointestinal Neoplasms / immunology*
  • Humans
  • Interferon-alpha / immunology*
  • Interferon-alpha / pharmacology*
  • Interleukin-10 / blood*
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Myeloid Cells / immunology*
  • Phosphorylation
  • STAT1 Transcription Factor / blood
  • STAT1 Transcription Factor / immunology
  • Signal Transduction


  • Interferon-alpha
  • Interleukin-6
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Interleukin-10