TLR7 Ligand Augments GM-CSF–Initiated Antitumor Immunity through Activation of Plasmacytoid Dendritic Cells

DOI PDF PubMed 被引用文献1件 参考文献42件 オープンアクセス
  • Megumi Narusawa
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Hiroyuki Inoue
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Chika Sakamoto
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Yumiko Matsumura
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Atsushi Takahashi
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Tomoko Inoue
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Ayumi Watanabe
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Shohei Miyamoto
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Yoshie Miura
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Yasuki Hijikata
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Yoshihiro Tanaka
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Makoto Inoue
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Koichi Takayama
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Toshihiko Okazaki
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Mamoru Hasegawa
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Yoichi Nakanishi
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan
  • Kenzaburo Tani
    Authors' Affiliations: 1Department of Molecular Genetics, Medical Institute of Bioregulation; 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; 3Department of Advanced Cell and Molecular Therapy and 4Center for Clinical and Translational Research, Kyushu University Hospital, Kyushu University, Fukuoka; and 5DNAVEC Corporation, Tsukuba, Japan

書誌事項

公開日
2014-06-01
資源種別
journal article
DOI
  • 10.1158/2326-6066.cir-13-0143
公開者
American Association for Cancer Research (AACR)

この論文をさがす

説明

<jats:title>Abstract</jats:title> <jats:p>Vaccination with irradiated granulocyte macrophage colony-stimulating factor (GM-CSF)–transduced autologous tumor cells (GVAX) has been shown to induce therapeutic antitumor immunity. However, its effectiveness is limited. We therefore attempted to improve the antitumor effect by identifying little-known key pathways in GM-CSF–sensitized dendritic cells (GM-DC) in tumor-draining lymph nodes (TDLN). We initially confirmed that syngeneic mice subcutaneously injected with poorly immunogenic Lewis lung carcinoma (LLC) cells transduced with Sendai virus encoding GM-CSF (LLC/SeV/GM) remarkably rejected the tumor growth. Using cDNA microarrays, we found that expression levels of type I interferon (IFN)–related genes, predominantly expressed in plasmacytoid DCs (pDC), were significantly upregulated in TDLN-derived GM-DCs and focused on pDCs. Indeed, mouse experiments demonstrated that the effective induction of GM-CSF–induced antitumor immunity observed in immunocompetent mice treated with LLC/SeV/GM cells was significantly attenuated when pDC-depleted or IFNα receptor knockout (IFNAR−/−) mice were used. Importantly, in both LLC and CT26 colon cancer–bearing mice, the combinational use of imiquimod with autologous GVAX therapy overcame the refractoriness to GVAX monotherapy accompanied by tolerability. Mechanistically, mice treated with the combined vaccination displayed increased expression levels of CD86, CD9, and Siglec-H, which correlate with an antitumor phenotype, in pDCs, but decreased the ratio of CD4+CD25+FoxP3+ regulatory T cells in TDLNs. Collectively, these findings indicate that the additional use of imiquimod to activate pDCs with type I IFN production, as a positive regulator of T-cell priming, could enhance the immunologic antitumor effects of GVAX therapy, shedding promising light on the understanding and treatment of GM-CSF–based cancer immunotherapy. Cancer Immunol Res; 2(6); 568–80. ©2014 AACR.</jats:p>

収録刊行物

  • Cancer Immunology Research

    Cancer Immunology Research 2 (6), 568-580, 2014-06-01

    American Association for Cancer Research (AACR)

被引用文献 (1)*注記

もっと見る

参考文献 (42)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ