Immunomodulation of ovarian clear cell carcinoma by targeting HNF-1 beta pathway
Project/Area Number |
15K10731
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Keio University |
Principal Investigator |
Fujita Tomonobu 慶應義塾大学, 医学部(信濃町), 助教 (20199334)
|
Co-Investigator(Kenkyū-buntansha) |
岩田 卓 慶應義塾大学, 医学部(信濃町), 講師 (30296652)
河上 裕 慶應義塾大学, 医学部(信濃町), 教授 (50161287)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 卵巣癌 / 免疫療法 / 卵巣明細胞腺癌 / 免疫抑制 / がん免疫療法 / 明細胞腺がん / がん微小環境 / 免疫抑制解除 / HNF-1β / 腫瘍内浸潤リンパ球 / 癌免疫抑制環境制御 |
Outline of Final Research Achievements |
We have evaluated immunopathology of human ovarian clear cell carcinoma (OCCC), which generally produces high amounts of immunosuppressive cytokines such as IL6 and IL8, which are correlated with poor prognoses. T cell infiltration in tumors is fewer in OCCC than that in serous ovarian cancers. We screened drug libraries and found twelve chemical compounds capable of inhibiting production of IL6 by OCCC cell lines. One of them epigenetically suppressed HNF-1β, an OCCC-specific transcriptional factor which we previously identified as the upstream for the high production of IL6 and IL8 from OCCC. Some of them also showed reversal of the immunosuppressive conditions in mice implanted with human OCCC cell lines. These results indicate that inhibitors on the HNF-1β-IL6/IL8 pathway may improve immunosuppressive conditions of OCCC and useful for combination immunotherapy for patients with OCCC.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Pilot study of WT1 peptide-pulsed dendritic cell vaccination with docetaxel in esophageal cancer2018
Author(s)
Tatsuo Matsuda, Hiroya Takeuchi, Toshiharu Sakurai, Shuhei Mayanagi, Eisuke Booka, Tomonobu Fujita, Hajime Higuchi, Junichi Taguchi, Yasuo Hamamoto, Hiromasa Takaishi, Hirofumi Kawakubo, Masato Okamoto, Makoto Sunamura, Yutaka Kawakami, Yuko Kitagawa.
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Journal Title
Oncology letters
Volume: 印刷中
Related Report
Peer Reviewed
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[Journal Article] Determination of poor prognostic immune features of tumour microenvironment in non-smoking patients with lung adenocarcinoma2017
Author(s)
Kinoshita T, Kudo-Saito C, Muramatsu R, Fujita T, Saito M, Nagumo H, Sakurai T, Noji S, Takahata E, Yaguchi T, Tsukamoto N, Hayashi Y, Kaseda K, Kamiyama I, Ohtsuka T, Tomizawa K, Shimoji M, Mitsudomi T, Asamura H, Kawakami Y.
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Journal Title
European Journal of Cancer
Volume: 86
Pages: 15-27
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Peptide-pulsed dendritic cell vaccine in combination with carboplatin and paclitaxel chemotherapy for stage IV melanoma.2017
Author(s)
Fukuda K, Funakoshi T, Sakurai T, Nakamura Y, Mori M, Tanese K, Tanikawa A, Taguchi J, Fujita T, Okamoto M, Amagai M, Kawakami Y.
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Journal Title
Melanoma Research.
Volume: in press
Issue: 4
Pages: 326-334
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Predictive biomarkers for the efficacy of peptide vaccine treatment: based on the results of a phase II study on advanced pancreatic cancer.2017
Author(s)
Shindo Y, Hazama S, Suzuki N, Iguchi H, Uesugi K, Tanaka H, Aruga A, Hatori T, Ishizaki H, Umeda Y, Fujiwara T, Ikemoto T, Shimada M, Yoshimatsu K, Takenouchi H, Matsui H, Kanekiyo S, Iida M, Koki Y, Arima H, Furukawa H, Ueno T, Yoshino S, Fujita T, Kawakami Y, Nakamura Y, Oka M, Nagano H.
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Journal Title
J Exp Clin Cancer Res.
Volume: 36
Issue: 1
Pages: 36-36
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer.2016
Author(s)
Kinoshita T, Muramatsu R, Fujita T, Nagumo H, Sakurai T, Noji S, Takahata E, Yaguchi T, Tsukamoto N, Kudo-Saito C, Hayashi Y, Kamiyama I, Ohtsuka T, Asamura H, Kawakami Y.
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Journal Title
Ann Oncol.
Volume: 27
Issue: 11
Pages: 2117-2123
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer.2015
Author(s)
Mayanagi S, Kitago M, Sakurai T, Matsuda T, Fujita T, Higuchi H, Taguchi J, Takeuchi H, Itano O, Aiura K, Hamamoto Y, Takaishi H, Okamoto M, Sunamura M, Kawakami Y, Kitagawa Y.
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Journal Title
Cancer Science
Volume: 106
Issue: 4
Pages: 397-406
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Aberrant Myosin 1b Expression Promotes Cell Migration and Lymph Node Metastasis of HNSCC.Mol2014
Author(s)
Ohmura G, Tsujikawa T, Yaguchi T, Kawamura N, Mikami S, Sugiyama J, Nakamura K, Kobayashi A, Iwata T, Nakano H, Shimada T, Hisa Y, Kawakami Y.
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Journal Title
Cancer Res. Epub ahead of print
Volume: 13
Issue: 4
Pages: 721-731
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] B-cell subsets possess different roles in colorectal cancer immune-microenvironment.2017
Author(s)
Budiman Kharma, Boryana Popivanova, Tomonobu Fujita, Shuji Mikami Shoichi Hazama, Kiyotaka Okuno, Ryo Matoba, Ichiro Takemasa, Shin Takahashi, Kota Ouchi, Chikashi Ichioka, Yutaka Kawakami.
Organizer
第76回日本癌学会学術総会
Related Report
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[Presentation] B-cell subsets possess different roles in colorectal cancer immune-microenvironment.2017
Author(s)
Budiman Kharma, Boryana Popivanova, Tomonobu Fujita, Hayashi Yuichiro, Mikami Shuji, suzuki Nobuoki, Nagano Hiroaki, Hazama Shoichi, Okuno Kiyotaka, Matoba Ryo, Takemasa Ichiro, Takahashi Shin Ouchi Kota, Ishioka Chikashi, Kawakami Yutaka.
Organizer
第21回日本がん免疫学会総会
Related Report
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