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Title
  • en IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4+ T cells
Creator
    • en Ohno, Yosuke
    • en Takahashi, Norihiko
    • en Ohtake, Junya
    • en Kaneumi, Shun
    • en Sumida, Kentaro
    • en Kawamura, Hideki
    • en Minagawa, Nozomi
    • en Shibasaki, Susumu
Accessrights open access
Rights
  • en The final publication is available at Springer via http://dx.doi.org/10.​1007/​s00262-015-1791-4
Subject
  • Other en Dendritic cells
  • Other en Antigen presentation
  • Other en HLA class II
  • Other en IL-12
  • Other en Helper T cells
  • NDC 490
Description
  • Abstract en Immunosuppression in tumor microenvironments critically affects the success of cancer immunotherapy. Here, we focused on the role of interleukin (IL)-6/signal transducer and activator of transcription (STAT3) signaling cascade in immune regulation by human dendritic cells (DCs). IL-6-conditioned monocyte-derived DCs (MoDCs) impaired the presenting ability of cancer-related antigens. Interferon (IFN)-γ production attenuated by CD4+ T cells co-cultured with IL-6-conditioned MoDCs corresponded with decreased DC IL-12p70 production. Human leukocyte antigen (HLA)-DR and CD86 expression was significantly reduced in CD11b+CD11c+ cells obtained from peripheral blood mononuclear cells (PBMCs) of healthy donors by IL-6 treatment and was STAT3 dependent. Arginase-1 (ARG1), lysosomal protease, cathepsin L (CTSL), and cyclooxygenase-2 (COX2) were involved in the reduction of surface HLA-DR expression. Gene expressions of ARG1, CTSL, COX2, and IL6 were higher in tumor-infiltrating CD11b+CD11c+ cells compared with PBMCs isolated from colorectal cancer patients. Expression of surface HLA-DR and CD86 on CD11b+CD11c+ cells was down-regulated, and T cell-stimulating ability was attenuated compared with PBMCs, suggesting that an immunosuppressive phenotype might be induced by IL-6, ARG1, CTSL, and COX2 in tumor sites of colorectal cancer patients. There was a relationship between HLA-DR expression levels in tumor tissues and the size of CD4+ T and CD8+ T cell compartments. Our findings indicate that IL-6 causes a dysfunction in human DCs that activates cancer antigen-specific Th cells, suggesting that blocking the IL-6/STAT3 signaling pathway might be a promising strategy to improve cancer immunotherapy.
Publisher en Springer
Date
    Issued2016-02
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/64455
Relation
  • isVersionOf DOI https://doi.org/10.1007/s00262-015-1791-4
  • PMID 26759006
Journal
    • PISSN 0340-7004
      • en Cancer immunology, immunotherapy
      • Volume Number65 Issue Number2 Page Start193 Page End204
File
Oaidate 2023-07-26