Analysis of escaping mechanism from immune system by microenvironment of cancer stem cells

• Project/Area Number: 15K14384
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Keio University
• Principal Investigator: Saya Hideyuki 慶應義塾大学, 医学部, 教授 (80264282)
• Co-Investigator(Kenkyū-buntansha): SUGIHARA Eiji 慶應義塾大学, 医学部, 特任助教 (50464996)
• Project Period (FY): 2015-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: がん幹細胞 / 腫瘍免疫 / 卵巣がん / 急性リンパ芽球性白血病 / 動物モデル

Outline of Final Research Achievements

In this study, we hypothesized that cancer stem cells is responsible for escaping from immune system against tumor formation. Our developed mice models with induced cancer stem cells (iCSCs) revealed that CD47, a cell surface molecule to block macrophage’s phagocytosis, is not required for escaping of ovarian iCSC from immune surveillance, suggesting that other molecules can be involved. Furthermore, analysis of leukemic iCSCs revealed that different driver oncogenes induce different mechanisms to escape from immune system during leukemogenesis. These results suggest that CSCs have the potential to regulate immune system.

Research Products

• [Journal Article] ALKR1275Q perturbs extracellular matrix, enhances cell invasion and leads to the development of neuroblastoma in cooperation with MYCN. (2016)
  • Author(s): Ueda T, Nakata Y, Yamasaki N, Oda H, Sentani K, Kanai A, Onishi N, Ikeda K, Sera Y, Honda ZI, Tanaka K, Sata M, Ogawa S, Yasui W, Saya H, Takita J, Honda H.
  • Journal Title: Oncogene. Volume: 無 Issue: 34 Pages: 4447-4458
  • DOI: 10.1038/onc.2015.519
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Periostin Is a Key Niche Component for Wound Metastasis of Melanoma. (2015)
  • Author(s): Fukuda K, Sugihara E, Ohta S, Izuhara K, Funakoshi T, Amagai M, Saya H.
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: e0129704-e0129704
  • DOI: 10.1371/journal.pone.0129704
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma. (2015)
  • Author(s): Adachi T, Kobayashi T, Sugihara E, Yamada T, Ikuta K, Pittaluga S, Saya H, Amagai M, Nagao K.
  • Journal Title: Nature Med. Volume: 21 Issue: 11 Pages: 1272-1279
  • DOI: 10.1038/nm.3962
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] がん幹細胞を標的とする新たながん治療開発の展望 (2015)
  • Author(s): 佐谷秀行
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 国立京都国際会館（京都府左京区）
  • Year and Date: 2015-10-29
  • Invited
• [Presentation] New mouse lymphoma model reveals the requirement for Fas downregulation in initiation and maintenance of lymphoma cells (2015)
  • Author(s): 杉原英志、橋本典愉、植野さやか、清水孝恒、佐谷秀行
  • Organizer: 第74回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] がん幹細胞の代謝不均一性 (2015)
  • Author(s): 佐谷秀行
  • Organizer: 第13回日本プロテオーム学会
  • Place of Presentation: くまもと森都心プラザ（熊本県熊本市）
  • Year and Date: 2015-07-23
  • Invited
• [Presentation] がん幹細胞の特性解析と標的治療 (2015)
  • Author(s): 佐谷秀行
  • Organizer: 第13回日本臨床腫瘍学会学術集会
  • Place of Presentation: 札幌市教育文化会館（北海道札幌市）
  • Year and Date: 2015-07-16
  • Invited
• [Presentation] がん幹細胞を標的とした治療戦略 (2015)
  • Author(s): 佐谷秀行
  • Organizer: 第25回日本サイトメトリー学会学術集会
  • Place of Presentation: ソラシティーカンファレンスセンター（東京都千代田区）
  • Year and Date: 2015-07-11
  • Invited
• [Presentation] New mouse model for mature B cell lymphoma revealing requirement for Fas downregulation in lymphomagenesis. (2015)
  • Author(s): Sugihara E, Hashimoto N, Ueno S, Saya H
  • Organizer: 20th Congress of European Hematology Association
  • Place of Presentation: Vienna, Austria.
  • Year and Date: 2015-06-11
  • Int'l Joint Research
• [Presentation] Novel mouse model for mature B cell lymphoma reveals the requirement for Fas downregulation in lymphomagenesis. (2015)
  • Author(s): Sugihara E, Hashimoto N, Ueno S, Saya H
  • Organizer: American Association for Cancer Research Annual meeting
  • Place of Presentation: Philadelphia, USA.
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Remarks] 慶應義塾大学 医学部 先端医科学研究所 遺伝子制御研究部門
  • URL: http://genereg.jp/index.html