Development of new treatment for endometrial cancer based on theanalysis of immune suppressive molecules

• Project/Area Number: 19591944
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: FUJITA Tomonobu Keio University, 医学部, 助教 (20199334)
• Co-Investigator(Kenkyū-buntansha): KAWAKAMI Yutaka 慶應義塾大学, 医学部, 教授 (50161287) ; AOKI Daisuke 慶應義塾大学, 医学部, 教授 (30167788)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 腫瘍抗原 / 子宮体癌 / 免疫抑制 / 分子標的薬 / PD-L1

Research Abstract

本研究では、子宮体癌における遺伝子異常・シグナル異常に基づいた癌細胞が作り出す免疫抑制機構の解明、その結果に基づいた新しい治療法開発の可能性を検討した。子宮体癌細胞株を用いて、免疫抑制性サイトカインと免疫抑制性膜分子の発現、子宮体癌細胞におけるシグナル経路の亢進を明らかにした。子宮体癌ではIL6、VEGF、TGFβ、PD-L1などの免疫抑制性分子が産生され、子宮体癌においても悪性黒色腫同様にこれら免疫抑制性分子を制御することによる免疫療法の開発の可能性が示された。

Research Products

• [Journal Article] Melanoma Differentiation-Associated Gene 5 is a Major Autoantigen (CADM-140) in Patients with Clinically Amyopathic Dermatomyosis and Rapidly Progressive Interstitial Lung Disease (2009)
  • Author(s): Sato S, Hoshino K, Satoh T, Fujita To, Kawakami Y, Fujita T, Kuwana M.
  • Journal Title: Rheumatology in press
  • Peer Reviewed
• [Journal Article] Cancer Metastasis is Accelerated through Immunosuppression during Snail-induced EMT of Cancer Cells (2009)
  • Author(s): Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y
  • Journal Title: Cancer Cell 15 Pages: 195-206
  • Peer Reviewed
• [Journal Article] Overexpression of class III beta-tubulin predicts good response to taxane-based chemotherapy in ovarian clear cell adenocarcinoma (2009)
  • Author(s): Aoki, et. al.
  • Journal Title: Clin Cancer Res 15 Pages: 1473-1480
  • Peer Reviewed
• [Journal Article] Dendritic cell based personalized immunotherapy based on cancer antigen research (2008)
  • Author(s): Kawakami Y, Fujita T, Kudo C, Sakurai T, Udagawa M, Hasegawa G, Ishida A, Kitagawa Y, Tanabe M, Saito M, Izumi Y, Kawamura M, Yaguchi T, Ueda Y, Hayashi E, Wang Q, Okada S, Tsukamoto N, Matsuzaki Y, Sumimoto H, Takeuchi H, Tanikawa A, Handa M, Amagai M, Kobayashi K, Ikeda Y, Azuma I, Kitajima M
  • Journal Title: Frontier in Bioscience 13 Pages: 1952-1958
• [Journal Article] Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6 (2008)
  • Author(s): Ueda R, Kinoshita E, Ito R, Kawase T, Kawakami Y, Toda M
  • Journal Title: Int J Cancer 122(10) Pages: 2274-2279
  • Peer Reviewed
• [Journal Article] Functional recovery after spinal cord injury in mice through activation of microglia and dendritic cells after IL-12 administration (2008)
  • Author(s): Yaguchi M, Ohta S, Toyama Y, Kawakami Y, Toda M
  • Journal Title: J Neurosci Res 86(9) Pages: 1972-1980
  • Peer Reviewed
• [Journal Article] Polyclonality of BRAF mutations in acquired melanocytic nevus and primary melanoma (2008)
  • Author(s): Lin J, Fujita T, Kawakami Y, et. al.
  • Journal Title: Cancer Res (in press)
  • Peer Reviewed
• [Journal Article] Clixucal significance of serum p 53 antibodies in patients with ulcerative colitis and its carcinogenesis (2008)
  • Author(s): Yoshizawa S, Fujita T, Kawakami Y, et. al.
  • Journal Title: Inflamm Bowel Dis 13 Pages: 865-873
  • Peer Reviewed
• [Journal Article] Clinical significance of serum p53 antibodies in patients with ulcerative colitis and its carcinogenesis (2007)
  • Author(s): Yoshizawa S, Matsuoka K, Inoue N, Takaishi H, Ogata H, Iwao Y, Mukai M, Fujita T, Kawakami Y, Hibi T
  • Journal Title: Inflamm Bowel Dis 13(7) Pages: 865-873
  • Peer Reviewed
• [Journal Article] Identification of a novel cancer-testis antigen CRT2 frequently expressed in various cancers using representational differential analysis (2007)
  • Author(s): Hayashi E, Matsuzaki Y, Kurihara S, Hasegawa G, Fujita T, Yaguchi T, Kageshita T, Sano M, Kawakami Y
  • Journal Title: Clin Cancer Res 13(21) Pages: 6267-6274
  • Peer Reviewed
• [Journal Article] Preferential expression and frequent IgG responses of a tumor antigen, SOX5, in glioma patients (2007)
  • Author(s): 6. Ueda R, Yoshida K, Kawase T, Kawakami Y, Toda M.
  • Journal Title: Int J Cancer 120(8) Pages: 1704-1711
  • Peer Reviewed
• [Journal Article] Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes (2007)
  • Author(s): Banno K, Yanokura M, Kawaguchi M, Kuwabara Y, Akiyoshi J, Kobayashi Y, Iwata T, Hirasawa A, Fujii T, Susumu N, Tsukazaki K, Aoki D.
  • Journal Title: Int J Oncol 31(4) Pages: 713-720
  • Peer Reviewed
• [Journal Article] Local activation of TGF-beta1 at endometriosis sites (2007)
  • Author(s): Komiyama S, Aoki D, Komiyama M, Nozawa S
  • Journal Title: J Reprod Med 52(4) Pages: 306-312
  • Peer Reviewed
• [Journal Article] Identification of a novel cancer-testis antigen CRT2 frequently expressed in various cancers using representational differential an alysis (2007)
  • Author(s): Hayashi E, Fujita T, Kawakami Y., et. al.
  • Journal Title: Clin Cancer Res 13 Pages: 6267-6274
  • Peer Reviewed
• [Presentation] 癌細胞におけるMAPKシグナル亢進による主要免疫逃避機構の解明 (2008)
  • Author(s): 谷口智憲、木藤健二、塚本信夫、桜井敏晴、藤田知信、持丸博史、丸山正太郎、里見良輔、井田陽介、岩田卓、住本秀敏、河上裕
  • Organizer: 第38回日本免疫学会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] エピジェネティック異常により発現抑制される子宮体がん関連癌抑制遺伝子のMPA療法における役割 (2008)
  • Author(s): 鶴田智彦, 井本逸勢, 平沢晃, 小崎健一, 阪埜浩司, 進伸幸, 青木大輔, 稲澤譲治
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 子宮体癌におけるhypoxia-inducible protein2(HIG2)蛋白発現 (2008)
  • Author(s): 津田浩史, 西村貞子, 進伸幸, 阪埜浩司, 片岡史夫, 青木大輔
  • Organizer: 第28回日本分子腫瘍マーカー研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-03
• [Presentation] 子宮体癌におけるhypoxia-inducibleprotein 2(HIG2)蛋白発現 (2008)
  • Author(s): 津田浩史, 西村貞子, 進伸幸, 阪埜浩司, 片岡史夫, 川村直樹, 青木大輔
  • Organizer: 第44回日本婦人科腫瘍学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-07-17
• [Presentation] 子宮体癌における分裂期キナーゼAurora-Aの発現と抗癌剤感受性との関連 (2008)
  • Author(s): 小林佑介, 阪埜浩司, 矢野倉惠, 秋好順子, 樋野牧子, 桑原佳子, 進伸幸, 塚崎克己, 青木大輔, 吉村泰典
  • Organizer: 第60回日本産科婦人科学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-04-12
• [Presentation] 進行子宮体癌の再発・予後因子としてのCOX-2とCD8陽性リンパ球についての検討 (2007)
  • Author(s): 末盛友浩, 進伸幸, 鶴田智彦, 市川義一, 野村弘行, 片岡史夫, 平澤晃, 冨永英一郎, 阪埜浩司, 鈴木淳, 青木大輔
  • Organizer: 第45回日本癌治療学会
  • Place of Presentation: 京都
  • Year and Date: 2007-10-24
• [Presentation] ヒトモノクローナル抗体HMMC-1を用いた子宮体癌に対する新規治療法の開発 (2007)
  • Author(s): 鈴木淳, 冨永英一郎, 山上亘, 笈川文子, 徐敬用, 野村弘行, 片岡史夫, 進伸幸, 石田功, 青木大輔
  • Organizer: 第27回日本分子腫瘍マーカー研究会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-02