2006 Fiscal Year Final Research Report Summary
enhancement of anti-tumor immunity in dendritic cell therapy toward gynecological malignancies
| Project/Area Number |
17591732
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kyoto University |
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Principal Investigator |
MANDAI Masaki Kyoto University, Gynecology and Obstetrics, Lecturer, 医学研究科, 講師 (80283597)
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| 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)
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| Project Period (FY) |
2005 – 2006
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| Keywords | gynecologic cancer / tumor immunity / PD-L1 / CD8+ T cell / K-562 |
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| 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
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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
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Research Products
(12 results)
