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enhancement of anti-tumor immunity in dendritic cell therapy toward gynecological malignancies

Research Project

Project/Area Number 17591732
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyoto University

Principal Investigator

MANDAI Masaki  Kyoto University, Gynecology and Obstetrics, Lecturer, 医学研究科, 講師 (80283597)

Co-Investigator(Kenkyū-buntansha) FUKUHARA Ken  Kyoto University, Gyn/Obstet, Assistant Professor, 医学研究科, 助手 (00362533)
FUJII Shingo  Kyoto University, Gyn/Obstet, Professor, 医学研究科, 教授 (30135579)
刈谷 方俊  京都大学, 医学研究科, 講師 (90243013)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsgynecologic cancer / tumor immunity / PD-L1 / CD8+ T cell / K-562 / 卵巣癌 / PD-L1 / 血管内皮前駆細胞 / 免疫療法
Research Abstract

Recent development in treatment modalities has achieved a marked improvement in the short-term survival of patients with ovarian cancer. Nevertheless, the long-term prognosis in advanced cases remains unsatisfactory, requiring a new paradigm in the treatment strategy. Various prognostic factors have been proposed and used clinically to predict the clinical course and to aid clinical decision-making in ovarian cancer patients. However, even using this system, prediction of the long-term prognosis, especially of late recurrence after remission remains difficult, suggesting a need to introduce other parameters such as sensitivity to chemotherapy and the strength of anti-tumor immune response. Several reports have shown the significance of tumor-infiltrating lymphocytes (TILs) as a prognostic factor in malignant tumors such as cutaneous melanoma, colorectal cancer, esophageal cancer, renal cancer, and ovarian cancer, suggesting that immunological parameters are significant and useful in as … More sessing the prognosis of cancer patients. However, there are few reports suggesting that a specific molecule can represent the strength of the host-tumor immunity. Therefore, in this project, we firstly analyzed if some of these immunological parameters are really related to the prognosis of the patient, and found that CD8+T cell number in the tumor as well as PD-L1 expression (ovarian cancer), or COX-2 expression (cervical adenocarcinoma) correlated with patient prognosis, indicating that tumor immunity is indeed important. Then, we tried to establish a method to acquire efficient tumor immunity toward ovarian cancer. Human dendiritic cells were collected from ovarian cancer patient blood with informed consent and anti-tumor immunity toward autologus ovarian cancer was measured in various conditions. Anti-tumor immunity was enhanced when DCs were co-cultured with K-562 cells transfected with and overexpressed Flt-3, suggesting that immunostimulatory signal from bystander cells can enhance tumor immunity. We are now preparing a mouse in vivo model of immunotherapy to deliver immunostimulatory signal using non-immune cell Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (17 results)

All 2007 2006 Other

All Journal Article (17 results)

  • [Journal Article] Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ Tlymphocytes are prognostic factors of human ovarian cancer.2007

    • Author(s)
      Hamanishi J, Mandai M, Iwasaki M, et al.
    • Journal Title

      Proc Natl Acad Sci U S A. 104

      Pages: 3360-3365

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] LH/hCG action and development of ovarian cancer-A short review on biological and clinical/epidemiological aspects.2007

    • Author(s)
      Mandai M, Konishi I, Kuroda H, Fujii S
    • Journal Title

      Mol Cell Endocrinol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression.2007

    • Author(s)
      Miyanishi M, Mandai M, Matsumura N, et al.
    • Journal Title

      Oncol Rep. 17

      Pages: 329-333

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer.2007

    • Author(s)
      Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, et al.
    • Journal Title

      Proc Natl Acad Sci U S A. 104(9)

      Pages: 3360-5

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] LH/hCG action and development of ovarian cancer-A short review on biological and clinical/epidemiological aspects.2007

    • Author(s)
      Mandai M, Konishi I, Kuroda H, Fujii S.
    • Journal Title

      Mol Cell Endocrinol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression.2007

    • Author(s)
      Miyanishi M, Mandai M, Matsumura N, Yamaguchi K, Hamanishi J, et al.
    • Journal Title

      Oncol Rep. 17(2)

      Pages: 329-33

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+T lymphocytes are prognostic factors of human ovarian cancer.2007

    • Author(s)
      Hamanishi J, Mandai M, Iwasaki M, Okazaki T, (5), Minato N, Honjo T, Fujii S
    • Journal Title

      Proc Natl Acad Sci U S A. 104(9)

      Pages: 3360-3365

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression.2007

    • Author(s)
      Miyanishi M, Mandai M, Matsumura N, (3), Takakura K, Fujii S
    • Journal Title

      Oncol Rep. 17(2)

      Pages: 329-333

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increased cyclooxygenase-2 expression is correlated with suppressed antitumor immunity in cervical adenocarcinomas.2006

    • Author(s)
      Chen TH, Fukuhara K, Mandai M, Matsumura N, et al.
    • Journal Title

      Int J Gynecol Cancer. 16

      Pages: 772-779

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Allogeneic MHC gene transfer enhances antitumor activity of allogeneic hematopoietic stem cell transplantation without exacerbating graft-versus-host disease.2006

    • Author(s)
      Ohashi M, Kobayashi A, Kushida M, Ikarashi Y, Mandai M, et al.
    • Journal Title

      Clin Cancer Res. 12

      Pages: 2208-2215

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oncogenic property of acrogranin in human uterine leiomyosarcoma : direct evidence of genetic contribution in in vivo tumorigenesis.2006

    • Author(s)
      Matsumura N, Mandai M, Miyanishi M, et al.
    • Journal Title

      Clin Cancer Res. 12

      Pages: 1402-1411

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Increased cyclooxygenase-2 expression is correlated with suppressed antitumor immunity in cervical adenocarcinomas.2006

    • Author(s)
      Chen TH, Fukuhara K, Mandai M, Matsumura N, Kariya M, et al.
    • Journal Title

      Int J Gynecol Cancer. 16(2)

      Pages: 772-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Allogeneic MHC gene transfer enhances antitumor activity of allogeneic hematopoietic stem cell transplantation without exacerbating graft-versus-host disease.2006

    • Author(s)
      Ohashi M, Kobayashi A, Hara H, Mandai M, Kitajima M, et al.
    • Journal Title

      Clin Cancer Res. 12(7 Pt 1)

      Pages: 2208-15

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oncogenic property of acrogranin in human uterine leiomyosarcoma : direct evidence of genetic contribution in in vivo tumorigenesis.2006

    • Author(s)
      Matsumura N, Mandai M, Miyanishi M, Fukuhara K, et al.
    • Journal Title

      Clin Cancer Res. 12(5)

      Pages: 1402-11

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oncogenic property of acrogranin in human uterine leiomyosarcoma : direct evidence of genetic contribution in in vivo tumorigenesis.2006

    • Author(s)
      Matsumura N, Mandai M, Miyanishi M, (4), Takakura K, Fujii S
    • Journal Title

      Clin Cancer Res. 12(5)

      Pages: 1402-1411

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Oncogenic property of acrogranin in human uterine leiomyosarcoma : direct evidence of genetic contribution in in vivo tumorigenesis2006

    • Author(s)
      Matsumura N, Mandai M, Miyanishi M, et al.
    • Journal Title

      Clin Cancer Res. 12(5)

      Pages: 1402-1411

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increased cyclooxygenase-2 expression is correlated with suppressed anti-tumor immunity in cervical adenocarcinoma.

    • Author(s)
      Chen-T.H, Fukuhara-K, Mandai-M
    • Journal Title

      Int.Journal of Gynecologiccal Cancer (in press)

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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