Establishment of combined cancer immunotherapy using neoantigen-induced mouse model
Project/Area Number |
18K16771
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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Research Institution | Shimane University |
Principal Investigator |
Ishibashi Tomoka 島根大学, 学術研究院医学・看護学系, 助教 (40643648)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | 癌免疫 / 癌免疫療法 / PD-1/PD-L1 / 複合的癌免疫療法 / 婦人科腫瘍 |
Outline of Final Research Achievements |
We reported that PD-1/PD-L1 inhibitors might be effective in patients with MSI-high endometrial cancers, and that MSI-high will be a potential biomarker for PD-1/PD-L1 inhibitors. In addition, we also reported that MSI-high is frequently observed in dedifferentiated endometrial cancers, and in undifferentiated cancer portions, the effect of immune checkpoint inhibitors can be expected. We speculated that combined treatment with anti-cancer drug and immune check point inhibitors may be effective for dedifferentiated endometrial cancers. Furthermore, we concluded that immune checkpoint inhibitors may be effective in patients with cervical adenocarcinoma with high PD-L1 expression. On the other hand, according to our genetic analysis in ovarian cancers, the frequency of MSI-high is estimated to be about 5%. Therefore, combined immune cancer treatment in combination with other anti-cancer drugs should be needed for patients with ovarian cancers.
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Academic Significance and Societal Importance of the Research Achievements |
卵巣癌では既に免疫チェックポイント阻害薬の奏功が報告されたが、治療効果が特に期待される集団については検討されていなかった。MSIまたはPOLE変異が関連する癌はmutation burden richと考えられるが、当科の研究では卵巣癌におけるMSI-highの頻度は5%程度であった。卵巣癌に対する免疫チェックポイント阻害薬の効果が期待されたが、他の薬剤と併用する複合的がん療法の必要性が示唆された。卵巣癌におけるこれらmutation burden richな腫瘍と免疫チェックポイント阻害薬の効果を検討することは、今後個別化した治療を選択する上で重要であり、今後臨床応用の可能性がある。
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Report
(4 results)
Research Products
(40 results)
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[Journal Article] Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer.2021
Author(s)
Kurose S, Nakayama K, Razia S, Ishikawa M, Ishibashi T, Yamashita H, Sato S, Sakiyama A, Yoshioka S, Kobayachi M, Nakayama S, Otsuki Y, Ishikawa N, Kyo S.
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Journal Title
Diseases (Basel, Switzerland)
Volume: 9
Issue: 1
Pages: 14-14
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.2020
Author(s)
Masako Ishikawa, Kentaro Nakayama, Kohei Nakamura, Hitomi Yamashita, Tomoka Ishibashi, Toshiko Minamoto, Kouji Iida, Sultana Razia, Noriyoshi Ishikawa, Satoru Nakayama, Yoshiro Otsuki, Satoru Kyo
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Journal Title
Archives of gynecology and obstetrics
Volume: 302
Issue: 1
Pages: 209-218
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic Value of Peripheral Blood Lymphocyte Telomere Length in Gynecologic Malignant Tumors.2020
Author(s)
Shanta K, Nakayama K, Ishikawa M, Ishibashi T, Yamashita H, Sato S, Sasamori H, Sawada K, Kurose S, Mahmud HM, Razia S, Iida K, Ishikawa N, Kyo S
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Journal Title
Cancers
Volume: 12
Issue: 6
Pages: 1469-1469
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mucinous borderline ovarian tumors with BRAF V600E mutation may have low risk for progression to invasive carcinomas2020
Author(s)
hnishi K, Nakayama K, Ishikawa M, Ishibashi T, Yamashita H, Nakamura K, Minamoto T, Iida K, Razia S, Ishikawa N, Kyo S.
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Journal Title
Arch Gynecol Obstet
Volume: 302
Issue: 2
Pages: 487-495
DOI
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Peer Reviewed / Open Access
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[Journal Article] High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients. Diagnostics (Basel). 2019;27;10(1). pii: E13.2019
Author(s)
Ishibashi T, Nakayama K, Razia S, Ishikawa M, Nakamura K, Yamashita H, Dey P, Iida K, Kurioka H, Nakayama S, Otsuki Y, Ishikawa N, Kyo S.
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Journal Title
Diagnostics (Basel).
Volume: 27;10(1)
Issue: 1
Pages: 13-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future.2019
Author(s)
Hitomi Yamashita, Kentaro Nakayama, Masako Ishikawa, Tomoka Ishibashi, Kohei Nakamura, Kiyoka Sawada, Yuki Yoshimura, Nagisa Tatsumi, Sonomi Kurose, Toshiko Minamoto, Kouji Iida, Sultana Razia, Noriyoshi Ishikawa, Satoru Ky
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Journal Title
International journal of molecular sciences
Volume: 20
Issue: 20
Pages: 1-1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinicopathological and biological analysis of PIK3CA mutation and amplification in cervical carcinomas.2019
Author(s)
Sultana Razia, Kentaro Nakayama, Kohei Nakamura, Tomoka Ishibashi, Masako Ishikawa, Toshiko Minamoto, Kouji Iida, Yoshiro Otsuki, Satoru Nakayama, Noriyoshi Ishikawa, Satoru Kyo
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Journal Title
Experimental and therapeutic medicine
Volume: 18
Pages: 2278-2284
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies).2019
Author(s)
Ruriko Ono, Kentaro Nakayama, Kohei Nakamura, Hitomi Yamashita, Tomoka Ishibashi, Masako Ishikawa, Toshiko Minamoto, Sultana Razia, Noriyoshi Ishikawa, Yoshiro Otsuki, Satoru Nakayama, Hideyuki Onuma, Hiroko Kurioka, Satoru Kyo
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Journal Title
International journal of molecular sciences
Volume: 20
Issue: 15
Pages: 1-1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] High frequency of POLE mutations in synchronous endometrial and ovarian carcinoma.2018
Author(s)
Ishikawa M, Nakayama K*, Nakamura K, Ono R, Yamashita H, Ishibashi T, Minamoto T, Iida K, Razia S, Ishikawa N, Kyo S.
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Journal Title
Hum Pathol
Volume: 18
Pages: 30424-30426
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report2018
Author(s)
Nakamura Kohei、Nakayama Kentaro、Minamoto Toshiko、Ishibashi Tomoka、Ohnishi Kaori、Yamashita Hitomi、Ono Ruriko、Sasamori Hiroki、Razia Sultana、Hossain Mohammad Mahmud、Kamrunnahar Shanta、Ishikawa Masako、Ishikawa Noriyoshi、Kyo Satoru
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Journal Title
International Journal of Molecular Sciences
Volume: 19
Issue: 4
Pages: 979-979
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Mutation analysis of Low grade serous ovarian carcinoma, serous borderline tumor and ovarian serous cystadenoma in Japanese population.2019
Author(s)
Ishibashi T, Nakayama K, Ishikawa M, Nakamura K, Sawada K, Yamashita H, Yoshimura Y, Iida K, Sultana R, Kyo S.
Organizer
第71回日本産科婦人科学会学術講演会
Related Report
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[Presentation] Microsatellite instability is a potential biomarker for immune checkpoint inhibitor(anti PD-1/PD-L1 antibody) in endometrial cancer2018
Author(s)
Hitomi Yamashita, Kentaro Nakayama, Masako Ishikawa, Tomoka Ishibashi, Kohei Nakamura, Kaori Ohnishi, Ruriko Ono, Hiroki Sasamori, Kohji Iida, Razia Sulutana, Toshiko Minamoto, Satoru Kyo
Organizer
第70回日本産科婦人科学会学術講演会
Related Report
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[Presentation] Mutation analysis of Low grade serous ovarian carcinoma(LGSOC), serous borderline tumor(SBT) and ovarian serous cystadenoma in Japanese populations.2018
Author(s)
Ishibashi T, Nakayama K, Yoshimura Y, Sawada K, Nakamura A, Ono R, Yamashita H, Nakamura K, Ishikawa M, Minamoto T, Kyo S
Organizer
IGCS/日本婦人科腫瘍学会
Related Report
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