Cancer Immunology, Immunotherapy

, Volume 60, Issue 9, pp 1269–1279

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

Authors

  • Bethany L. Mundy-Bosse
    • Department of Integrated Biomedical SciencesThe Ohio State University
    • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
  • Gregory S. Young
    • The Center for BiostatisticsThe Ohio State University
    • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
  • Todd Bauer
    • Department of Internal MedicineThe Ohio State University
    • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
  • Elaine Binkley
    • Department of Internal MedicineThe Ohio State University
    • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
  • Mark Bloomston
    • Department of SurgeryThe Ohio State University
    • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
  • Matthew A. Bill
    • Department of Internal MedicineThe Ohio State University
    • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
  • Tanios Bekaii-Saab
    • Department of Internal MedicineThe Ohio State University
    • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
    • Department of SurgeryThe Ohio State University
    • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
    • Department of Internal MedicineThe Ohio State University
    • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Original article

DOI: 10.1007/s00262-011-1029-z

Cite this article as:
Mundy-Bosse, B.L., Young, G.S., Bauer, T. et al. Cancer Immunol Immunother (2011) 60: 1269. doi:10.1007/s00262-011-1029-z

Abstract

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+HLADRCD11b+CD15+ and CD33+HLADR−/lowCD14+ MDSC subsets were also elevated in patients versus normal donors (P < 0.0001). Plasma IL-6 was correlated with CD33+HLADRCD15+ MDSC (P = 0.008) and IL-10 with CD33+HLADRCD15 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+HLADRCD15 MDSC subset was associated with reduced overall survival (P = 0.049), while an increased percentage of the CD33+HLADR−/lowCD14+ 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.

Keywords

Myeloid-derived suppressor cellImmune suppressionInterleukin-6Interleukin-10

Copyright information

© Springer-Verlag 2011