Increased soluble CD155 in the serum of cancer patients

• Project/Area Number: 16K14629
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: University of Tsukuba
• Principal Investigator: Shibuya Kazuko 筑波大学, 医学医療系, 准教授 (00302406)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 免疫系受容体 / 腫瘍マーカー / 免疫学 / 腫瘍免疫 / ヒト化マウス / 免疫逃避 / 免疫受容体 / 分子標的療法

Outline of Final Research Achievements

DNAM-1 plays an important role in the recognition of tumor cells and their lysis by CTL and NK cells. Although the DNAM-1 ligand CD155 is ubiquitously expressed in various tissues, many tumors significantly upregulate the expression of CD155. We demonstrated that the interaction of DNAM-1 on CTL and NK cells and CD155 on tumors was involved in mouse tumor immunity. However, unlike those in mice, human tissues also express soluble isoforms of CD155 (sCD155) that lack the transmembrane region. Here, we show that sCD155 levels were significantly higher in the sera of patients with cancers than in sera from healthy donors. In addition, the sCD155 levels were significantly higher in patients with advanced stage disease than in patients in those with early stage disease. Moreover, the sCD155 levels were significantly decreased after surgical resection of cancers. Thus, sCD155 level in serum may be potentially useful as a biomarker for cancer development and progression.

Research Products

• [Journal Article] Improved protocol for the isolation of naive follicular dendritic cells (2016)
  • Author(s): Sato K, Honda SI, Shibuya A, Shibuya K
  • Journal Title: Mol Immunol Volume: 78 Pages: 140-145
  • DOI: 10.1016/j.molimm.2016.09.011
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Activation of murine invariant NKT cells promotes susceptibility to candidiasis by IL-10-induced modulation of phagocyte antifungal activity (2016)
  • Author(s): Haraguchi N, Kikuchi N, Morishima Y, Matsuyama M, Sakurai H, Shibuya A, Shibuya K, Taniguchi M, Ishii Y
  • Journal Title: Eur J Immunol Volume: 46 Issue: 7 Pages: 1691-1703
  • DOI: 10.1002/eji.201545987
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Soluble DNAM-1, as a predictive biomarker for acute graft-versus-host disease (2016)
  • Author(s): Kanaya M, Shibuya K, Hirochika R, Kanemoto M, Ohashi K, Okada M, Wagatsuma Y, Cho Y, Kojima H, Teshima T, Imamura M, Sakamaki H, Shibuya A.
  • Journal Title: PLoS ONE Volume: 11 Issue: 6 Pages: e0154173-e0154173
  • DOI: 10.1371/journal.pone.0154173
  • NAID: 120007129409
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling (2016)
  • Author(s): Honda S, Sato K, Totsuka N, Fujiyama S, Fujimoto M, Miyake K, Nakahashi-Oda C, Tahara-Hanaoka S, Shibuya K, Shibuya A
  • Journal Title: Nat Commun Volume: 7 Issue: 1 Pages: 1-10
  • DOI: 10.1038/ncomms11498
  • NAID: 120007135503
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Increased soluble CD155 in the serum of cancer patients (2016)
  • Author(s): Iguchi-Manaka A, Okumura G, Kojima H, Cho Y, Hirochika R, Bando H, Sato T, Yoshikawa H, Hara H, Shibuya A, Shibuya K.
  • Journal Title: PLoS One Volume: 11(4) Issue: 4 Pages: 1-12
  • DOI: 10.1371/journal.pone.0152982
  • NAID: 120007135543
  • Peer Reviewed / Open Access
• [Presentation] Involvement of DNAM-1 (CD226) expressed on small peritoneal macrophages in antigen presentation. (2016)
  • Author(s): Vo AV, Takenaka E, Yamashita-Kanemaru Y, Shibuya A, Shibuya K.
  • Organizer: 第45回日本免疫学会総会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Development of molecular targeted therapy for human acute GVHD in humanized mice (2016)
  • Author(s): Okumura G, Abe F, Ito M, Shibuya A, Shibuya K
  • Organizer: 第45回日本免疫学会総会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Apoptotic epithelial cells control the abundance of regulatory T cells at barrier surfaces. (2016)
  • Author(s): Nakahashi-Oda C, Udayanga K. G. S, Nakamura Y, Nakazawa Y, Totsuka N, Miki H, Iino S, Tahara-Hanaoka S, Honda S, Shibuya K, Shibuya A
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne (Australia)
  • Year and Date: 2016-08-22
  • Int'l Joint Research
• [Presentation] CD155 (PVR/Necl5) mediates a costimulatory signal in CD4+ T cells and regulates allergic inflammation. (2016)
  • Author(s): Yamashita-Kanemaru Y, Bernhardt G, Shibuya A, Shibuya K.
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne (Australia)
  • Year and Date: 2016-08-22
  • Int'l Joint Research
• [Presentation] “今後の基礎医学教育のあり方”に関するアンケート調査 (2016)
  • Author(s): 岸美紀子、井内康輝、坂井建雄、高桑雄一、堤寛、柳澤輝行、鯉淵典之、渋谷和子、中島昭、熊ノ郷淳
  • Organizer: 第48回日本医学教育学会大会
  • Place of Presentation: 大阪市立大学（大阪府大阪市）
  • Year and Date: 2016-07-29
• [Presentation] ヒト化マウスを用いた抗ヒトDNAM-1抗体によるヒト急性GVHDの治療法開発 (2016)
  • Author(s): 渋谷和子、阿部史枝、伊藤守、渋谷彰
  • Organizer: 第8回血液疾患免疫療法学会学術集会
  • Place of Presentation: 北海道大学（北海道札幌市）
• [Presentation] 筑波大学における臨地実習前OSCEの開発に向けた取組 (2016)
  • Author(s): 會田雄一、山内一由、上妻行則、渋谷和子、上杉憲子、中川嘉、吉田文代、山下年晴、小池朗、二宮治彦
  • Organizer: 第11回日本臨床検査学教育学会学術大会
  • Place of Presentation: 神戸常盤大学（兵庫県神戸市）
• [Patent(Industrial Property Rights)] 抗ヒトＤＮＡＭ－１モノクローナル抗体及びその使用 (2016)
  • Inventor(s): 渋谷彰、渋谷和子、阿部史枝、広近玲、奥村元紀
  • Industrial Property Rights Holder: 渋谷彰、渋谷和子、阿部史枝、広近玲、奥村元紀
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-084170
  • Filing Date: 2016-04-20