The elucidation of the mechanisms of sensitivity and resistance to anti VEGF antibodies in ovarian cancer
| Project/Area Number |
15H04309
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
馬場 長 京都大学, 医学研究科, 准教授 (60508240)
濱西 潤三 京都大学, 医学研究科, 講師 (80378736)
小西 郁生 京都大学, 医学研究科, 名誉教授 (90192062)
松村 謙臣 京都大学, 医学研究科, 准教授 (20452336)
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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 |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 抗VEGF抗体 / 感受性 / 耐性 / 免疫抑制 / 骨髄由来免疫抑制性細胞(MDSCs) / GM-CSF / 抗VEGF抗 / Gr-1 / CD8 / 骨髄由来免疫抑制性細胞 / ピモニダゾール / 低酸素状態 / ＶＥＧＦ抗体 / PD-1抗体 / 耐性遺伝子 / 抗VEGF抗体治療 / Gr-1陽性細胞 / CD8陽性リンパ球 / 薬剤反応性 / 抗ＶＥＧＦ抗体 / 卵巣癌 / 耐性獲得機構 / 発現マイクロアレイ / バイオマーカー |
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| Outline of Final Research Achievements |
The elucidation of the mechanism underlying the development of resistance to anti-VEGF antibodies in ovarian cancer is urgently required. We found that immunosuppression in the tumor microenvironment is associated with resistance to anti-VEGF therapy with the use of preclinical models. Anti-VEGF therapy induced myeloid-derived suppressor cells (MDSCs), which suppressed lymphocyte activity. Anti-VEGF therapy induced tumor hypoxia, which up-regulated the GM-CSF expression in tumor cells and recruited MDSCs into the tumor site. The blockade of GM-CSF signaling improved tumor immunity and enhanced the efficacy of anti-VEGF therapy. Treatments targeting MDSCs induced by VEGF signaling may improve prognosis in patients with high-grade serous ovarian cancer. The development of therapies combining anti-VEGF therapy with drugs targeting tumor immunity is expected.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Combination of Aprepitant, Azasetron, and Dexamethasone as Antiemetic Prophylaxis in Women with Gynecologic Cancers Receiving Paclitaxel/Carboplatin Therapy.2017
Author(s)
Koshiyama M, Matsumura N, Imai S, Yamanoi K, Abiko K, Yoshioka Y, Yamaguchi K, Hamanishi J, Baba T, Konishi I.
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Journal Title
Med Sci Monit.
Volume: 23
Pages: 826-33
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Expression of VEGF in ovarian cancer suppresses tumor immunity through recruitment of myeloid derived suppressor cells2015
Author(s)
Naoki Horikawa, Kaoru Abiko, Noriomi Matsumura, Junzo Hamanishi, Susan K Murphy, Tsukasa Baba, Ken Yamaguchi, Masafumi Koshiyama, Ikuo Konishi
Organizer
An AACR Special Conference on Advances in Ovarian Cancer Research
Place of Presentation
Hyatt Regency Orland, Orland, FL
Year and Date
2015-10-17
Related Report
Int'l Joint Research
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