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

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• 作者：1. Department of Integrated Biomedical Sciences ; The Ohio State University ; Columbus ; OH ; USA2. The Center for Biostatistics ; The Ohio State University ; Columbus ; OH ; USA3. Department of Internal Medicine ; The Ohio State University ; 302B Comprehensive Cancer Center/Wiseman Hall ; 400?W. 12th Ave ; Columbus ; OH 43210 ; USA4. Department of Surgery ; The Ohio State University ; N911 Doan Hall ; 410?W. 10th Ave ; Columbus ; OH 43210 ; USA5. Arthur G. James Cancer Hospital and Richard J. Solove Research Institute ; Columbus ; OH 43210 ; USA
• 关键词：Myeloid ; derived suppressor cell – Immune suppression – Interleukin ; 6 – Interleukin ; 10
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2011
• 出版时间：September 2011
• 年：2011
• 卷：60
• 期：9
• 页码：1269-1279
• 全文大小：429.9 KB
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• 作者单位：http://www.springerlink.com/content/1442l47313744517/
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

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?/lowCD14+ 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?/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.