Elucidation of the mechanism of immunosuppression by mesenchymal stem cells in cancer microenvironments

• Project/Area Number: 21890247
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Keio University
• Principal Investigator: YAGUCHI Tomonori Keio University, 医学部, 助教 (40424163)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,652,000 (Direct Cost: ¥2,040,000、Indirect Cost: ¥612,000); Fiscal Year 2010: ¥1,261,000 (Direct Cost: ¥970,000、Indirect Cost: ¥291,000); Fiscal Year 2009: ¥1,391,000 (Direct Cost: ¥1,070,000、Indirect Cost: ¥321,000)
• Keywords: 間葉系幹細胞 / 腫瘍免疫回避 / がん免疫療法 / 癌免疫療法 / 腫瘍間質 / 樹状細胞 / 線維芽細胞

Research Abstract

In this study, we evaluated the immunological roles of mesenchymal stem cells (MSC) in cancer microenvironment. GFP chimeric mouse models showed that bone marrow-derived MSC migrated to caner tissues and augmented the tumor growth. Human MSC inhibited dendritic cells functions through the production of a variety of immunosuppressive cytokines such as IL6 and VEGF. These results suggested that MSC induced caner immune evasion in the cancer microenvironment and can be an attractive target for the restoration of immune competence of cancer patients.

Research Products

• [Journal Article] The mechanisms of cancer immunoescape and development of overcoming strategies. (2011)
  • Author(s): Yaguchi T, Sumimoto H, Kudo-Saito C, Tsukamoto N, Ueda R, Iwata-Kajihara T, Nishio H, Kawamura N, Kawakami Y.
  • Journal Title: Int J Hematol 93 Pages: 294-300
  • NAID: 10029533724
  • URL: http://www.springerlink.com/content/c478p246673x144p/fulltext.pdf
  • Peer Reviewed
• [Journal Article] The mechanisms of cancer immunoescape and development of overcoming strategies. (2011)
  • Author(s): Yaguchi T, Sumimoto H, Kudo-Saito C, Tsukamoto N, Ueda R, Iwata-Kajihara T, Nishio H, Kawamura N, Kawakami Y
  • Journal Title: International Journal of Hematology Volume: 93 Pages: 294-300
  • NAID: 10029533724
  • Peer Reviewed
• [Journal Article] 樹状細胞制御による抗腫瘍免疫増強 (2011)
  • Author(s): 川村直, 宮崎潤一郎, 梶原-岩田知子, 谷口智憲, 河上裕
  • Journal Title: 胆と膵 Volume: 32 Pages: 123-127
• [Journal Article] SEREX法による腫瘍抗原の単離と免疫療法への応用 (2011)
  • Author(s): 宮崎潤一郎, 川村直, 梶原-岩田知子, 谷口智憲, 河上裕
  • Journal Title: 細胞 Volume: 43 Pages: 4-7
• [Journal Article] 癌細胞由来エクソソームによる免疫系への作用とその臨床応用 (2010)
  • Author(s): 植田良, LiQian, 中村公子, 谷口智憲, 宮崎潤一郎, 川村直, 河上裕
  • Journal Title: 実験医学 Volume: 29 Pages: 410-414
• [Journal Article] Emerging concepts in biomarker discovery ; The US-Japan workshop on immunological molecular markers in oncology. (2009)
  • Author(s): Tahara H, Yaguchi T, et al.
  • Journal Title: J Transl Med. 7 Pages: 45-45
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/19534815
  • Peer Reviewed
• [Presentation] Immunosuppressions by human cancer cells and their control for effective immunotherapy. (2010)
  • Author(s): Yutaka Kawakami, Chie Kudo-saito, Hidetoshi Sumimoto, Nobuo Tsukamoto, Ryo Ueda, Naoshi Kawamura, Tomonori Yaguchi
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2010-09-24
• [Presentation] Increased cell motility and immunosuppression ability of human melanoma via ectopically expressed histatin-1 (2010)
  • Author(s): Tomonori Yaguchi, Tomoki Kurihara, Yasufumi Goto, Yuki Ito, Kenji Morii, Hidetoshi Sumimoto, Yutaka Kawakami
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-24
• [Presentation] Blockade of activated NF-kB in cancer and immune cells mayeliminate immunosuppressive state in human ovarian cancer (2010)
  • Author(s): Hiroshi Nishio, Tomonori Yaguchi, Tomonobu Fujita, Kazuo Umezawa, Takashi Iwata, Takuma Fujii, Hidetoshi Sumimoto, Daisuke Aoki, Yutaka Kawakami
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-24
• [Presentation] MicroRNA-222 is a potential target for developing blood-based diagnostic methods and treatment of malignant glioma. (2010)
  • Author(s): Ryo Ueda, Qian Li, Tomonori Yaguchi, Nobuyoshi Kosaka, Tomonobu Fujita, Hideho Okada, Takahiro Ochiya, Yutaka Kawakami
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-22
• [Presentation] Possible improvement of cancer immunotherapy based on thaanalyses of anti-tumor immune responses in human. (2010)
  • Author(s): Yutaka Kawakami, Chie kudo-Saito, Hidetoshi Sumimoto, Ryo Ueda, Nobuo Tsukamoto, Tomonobu Fujita, Toshiharu Sakurai, Tomonori Yaguchi
  • Organizer: 金沢国際がん生物学シンポジウム
  • Place of Presentation: KKRホテル金沢
  • Year and Date: 2010-08-29
• [Presentation] Immune escape of human melanoma via activated Wnt/β-catenin signaling. (2010)
  • Author(s): Yaguchi T, Goto Y, Kido K, Mochimaru H, Sakurai T, Tsukamoto N, Kudo-Saito C, Fujita T, Sumimoto H, Kawakami Y.
  • Organizer: 14^<th> International Congress of Immunology 2010
  • Place of Presentation: Kobe International Convention Center
  • Year and Date: 2010-08-25
• [Presentation] Reversal of cancer induced immunosuppression by targeting altered signaling molecules in cancer cells and immune cells. (2010)
  • Author(s): Yutaka Kawakami, Hidetoshi sumimoto, Tomoko Iwata-Kajihara, Tomonori Yaguchi, Naoshi Kawamura, Chie Kudo-Saito, Nobuo Tsukamoto
  • Organizer: 14thInternational Congress of Immunology 2010
  • Place of Presentation: Kobe International Convention Center
  • Year and Date: 2010-08-25
• [Presentation] Immune escape of human melanoma via activated Wnt/β-catenin signaling. (2010)
  • Author(s): Tomonori Yaguchi, Yasufumi Goto, Kenji Kido, Hiroshi Mochimaru, Toshiharu Sakurai, Nobuo Tsukamoto, Chie Kudo-Saito, Tomonobu Fujita, Hidetoshi Sumimoto, Yutaka Kawakami
  • Organizer: 14thInternational Congress of Immunology 2010
  • Place of Presentation: Kobe International Convention Center
  • Year and Date: 2010-08-25
• [Presentation] Immunosuppression by human cancer cells and its control for effective immunotherapy. (2010)
  • Author(s): Yutaka kawakami, Chie Kudo-Saito, Hidetoshi Sumimoto, Nobuo Tsukamoto, Ryo Ueda, Tomonori Yaguchi.
  • Organizer: 14thInternational Congress of Immunology 2010
  • Place of Presentation: Kobe International Convention Center
  • Year and Date: 2010-08-24
• [Presentation] シンポジウム2「次世代がん免疫療法の開発に向けた基礎・応用研究「がん免疫逃避機構とその制御」 (2010)
  • Author(s): 河上裕、住本秀敏、工藤千恵、塚本信夫、植田良、梶原知子、川村直,谷口智憲,
  • Organizer: 第14回日本がん免疫学会
  • Place of Presentation: KKRホテル熊本
  • Year and Date: 2010-07-23
• [Presentation] 悪性黒色腫および樹状細胞でのWnt/β-cateninシグナル亢進はがん微小環境での免疫抑制に関与する (2010)
  • Author(s): 谷口智憲、守井賢二、西尾浩、桜井敏晴、塚本信夫、工藤千恵、藤田知信、河上裕
  • Organizer: 第14回日本がん免疫学会
  • Place of Presentation: KKRホテル熊本
  • Year and Date: 2010-07-23
• [Presentation] 卵巣癌におけるNF-κBシグナルの亢進は、IL-6の産生およびMDSCの誘導により、免疫抑制に関与する (2010)
  • Author(s): 西尾浩、谷口智憲、岩田卓、桜井敏晴、塚本信夫、工藤千恵、藤田知信、河上裕
  • Organizer: 第14回日本がん免疫学会
  • Place of Presentation: KKRホテル熊本
  • Year and Date: 2010-07-23
• [Presentation] MicroRNA-222 is a potential target for developing blood-based biomarker assay and treatment of malignant glioma. (2010)
  • Author(s): Ryo Ueda, Li Qian, Tomonori Yaguchi, Nobuyoshi Kosaka, Tomonobu Fujita, Hideho Okada, Takahiro Ochiya, Yutaka Kawakami
  • Organizer: 第16回日本遺伝子治療学会
  • Place of Presentation: 栃木県総合文化センター
  • Year and Date: 2010-07-01
• [Presentation] MAPK signaling is a potential target for improvement of immunotherapy through reversal of immunosuppressive tumor microenvironment. (2009)
  • Author(s): 谷口智憲、岩田-梶原知子、川村直、工藤-斉藤千恵、住本秀敏、河上裕
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪