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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

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タイトル: 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
著者: Ohno, Yosuke 著作を一覧する
Kitamura, Hidemitsu 著作を一覧する
Takahashi, Norihiko 著作を一覧する
Ohtake, Junya 著作を一覧する
Kaneumi, Shun 著作を一覧する
Sumida, Kentaro 著作を一覧する
Homma, Shigenori 著作を一覧する
Kawamura, Hideki 著作を一覧する
Minagawa, Nozomi 著作を一覧する
Shibasaki, Susumu 著作を一覧する
Taketomi, Akinobu 著作を一覧する
キーワード: Dendritic cells
Antigen presentation
HLA class II
Helper T cells
発行日: 2016年 2月
出版者: Springer
誌名: Cancer immunology, immunotherapy
巻: 65
号: 2
開始ページ: 193
終了ページ: 204
出版社 DOI: 10.1007/s00262-015-1791-4
抄録: 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.
Rights: The final publication is available at Springer via​1007/​s00262-015-1791-4
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 北村 秀光


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