An exploration of novel immunosuppressive factors by using immunological functional genome screening and development of new treatment strategy in ovarian cancer

• Project/Area Number: 26670723
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: HAMANISHI Junzo 京都大学, 医学(系)研究科(研究院), 助教 (80378736)
• Co-Investigator(Kenkyū-buntansha): KONISHI Ikuo 京都大学, 大学院医学研究科, 教授 (90192062) ; MATSUMURA Noriomi 京都大学, 大学院医学研究科, 准教授 (20452336) ; ABIKO Kaoru 京都大学, 大学院医学研究科, 准教授 (20508246)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 卵巣がん / がん免疫抑制 / 機能ゲノミクス / 免疫療法 / がん免疫逃避 / がん免疫逃避機構 / 卵巣癌 / 免疫ゲノミクス

Outline of Final Research Achievements

We detected several immune suppressive genes, by using immunological functional-genome -screening for exploring a novel factors related to cancer immune escape in ovarian cancer. Some of these genes-transduced ovarian cancer cell line showed immunosuppressive function with co-cultured CD8+T cells. Therefore these data suggested that we found one of novel immunosuppressive mechanism in ovarian cancer via these genes. Hereafter, we will confirm this immuno- mechanism with in vivo mouse ovarian cancer model.

Research Products

• [Journal Article] Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes. (2016)
  • Author(s): Murakami R, Matsumura N, Mandai M, Yoshihara K, Tanabe H, Nakai H, Yamanoi K, Abiko K, Yoshioka Y, Hamanishi J, Yamaguchi K, Baba T, Koshiyama M, Enomoto T, Okamoto A, Murphy SK, Mori S, Mikami Y, Minamiguchi S, Konishi I.
  • Journal Title: Am J Pathol. Volume: 未
  • Peer Reviewed
• [Journal Article] Anti-PD-L1/PD-1 immune therapies in ovarian cancer: basic mechanism and future clinical application. (2016)
  • Author(s): Mandai M, Hamanishi J, Abiko K, Matsumura N, Baba T, Konishi I.
  • Journal Title: Int J Clin Oncol. Volume: 未
  • Peer Reviewed
• [Journal Article] PD-1/PD-L1 blockade in cancer treatment: perspectives and issues. (2016)
  • Author(s): Hamanishi J, Mandai M, Matsumura N, Abiko K, Baba T, Konishi I.
  • Journal Title: Int J Clin Oncol Volume: 未
  • Peer Reviewed
• [Journal Article] Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer. (2015)
  • Author(s): Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, Yamaguchi K, Horikawa N, Hosoe Y, Murphy SK, Konishi I, Mandai M.
  • Journal Title: Cancer Res. Volume: 75 Issue: 23 Pages: 5034-5045
  • DOI: 10.1158/0008-5472.can-14-3098
  • Peer Reviewed
• [Journal Article] Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients. (2015)
  • Author(s): Horikawa N, Baba T, Matsumura N, Murakami R, Abiko K, Hamanishi J, Yamaguchi K, Koshiyama M, Yoshioka Y, Konishi I.
  • Journal Title: BMC Cancer. Volume: 15 Pages: 739-739
  • NAID: 120005749961
  • Peer Reviewed
• [Journal Article] Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. (2015)
  • Author(s): Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, Kanai M, Mori Y, Matsumoto S, Chikuma S, Matsumura N, Abiko K, Baba T, Yamaguchi K, Ueda A, Hosoe Y, Morita S, Yokode M, Shimizu A, Honjo T, Konishi I.
  • Journal Title: J Clin Oncol. Volume: 33 Pages: 4015-4022
  • Peer Reviewed
• [Journal Article] Metabolic alterations caused by HNF1β expression in ovarian clear cell carcinoma contribute to cell survival. (2015)
  • Author(s): Amano Y, Mandai M, Baba T, Hamanishi J, Yoshioka Y, Matsumura N, Konishi I.
  • Journal Title: Oncol Lett. Volume: 6 Pages: 26002-26017
  • Peer Reviewed
• [Journal Article] 【最新 がん免疫療法 抗PD-1抗体、CAR-T細胞療法から、Neoantigenを標的としたがん制御機構まで】 免疫チェックポイントの基礎とがん免疫療法への開発 (2015)
  • Author(s): 濱西 潤三, 万代 昌紀, 小西 郁生
  • Journal Title: 実験医学 Volume: 33 Pages: 2193-2200
  • Peer Reviewed
• [Journal Article] 【新たな時代を迎えたがん免疫療法】 免疫チェックポイント阻害療法の現状と展望 (2015)
  • Author(s): 濱西 潤三, 万代 昌紀, 小西 郁生
  • Journal Title: Medical Science Digest Volume: 41 Pages: 287-290
• [Journal Article] 【女性がん医療の最前線】卵巣癌治療 (2015)
  • Author(s): 濵西潤三, 万代昌紀, 松村謙臣, 小西郁生
  • Journal Title: Bio Clinica Volume: 16 Pages: 28-32
• [Journal Article] IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer (2015)
  • Author(s): Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, Yoshioka Y, Baba T, Konishi I, Mandai M
  • Journal Title: British Journal of Cancer Volume: 未確定 Issue: 9 Pages: 1501-1509
  • DOI: 10.1038/bjc.2015.101
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-a potential therapeutic target. (2015)
  • Author(s): Peng J, Yoshioka Y, Mandai M, et al
  • Journal Title: Mol Carcinog Volume: Epub ahead of print Issue: 4 Pages: 1-11
  • DOI: 10.1002/mc.22283
  • Peer Reviewed / Open Access
• [Journal Article] Invasion of uterine cervical squamous cell carcinoma cells is facilitated by locoregional interaction with cancer-associated fibroblasts via activating transforming growth factor-beta. (2015)
  • Author(s): Nagura M, Matsumura N, Baba T, Murakami R, Kharma B, Hamanishi J, Yamaguchi K, Abiko K, Koshiyama M, Mandai M, et al.
  • Journal Title: Gynecol Oncol Volume: 136 Issue: 1 Pages: 104-111
  • DOI: 10.1016/j.ygyno.2014.11.075
  • Peer Reviewed / Open Access
• [Journal Article] 話題の疾患と治療 免疫チェックポイントPD-1経路を標的とするがん治療への臨床応用(解説) (2015)
  • Author(s): 濱西 潤三*, 万代 昌紀, 小西 郁生
  • Journal Title: 感染・炎症・免疫 Volume: 44 Pages: 387-389
• [Journal Article] Clinical approaches to treating papillary squamous cell carcinoma of the uterine cervix. (2014)
  • Author(s): Nagura M, Koshiyama M, Matsumura N, Kido A, Baba T, Abiko K, Hamanishi J, Yamaguchi K, Mikami Y, Konishi I.
  • Journal Title: BMC Cancer Volume: 14 Issue: 1 Pages: 784-784
  • DOI: 10.1186/1471-2407-14-784
  • Peer Reviewed / Open Access
• [Journal Article] STAT1 drives tumor progression in serous papillary endometrial cancer. (2014)
  • Author(s): Kharma B, Baba T, Matsumura N, Kang HS, Hamanishi J, Murakami R, McConechy MM, Leung S, Yamaguchi K, Hosoe Y, Yoshioka Y, Murphy SK, Mandai M, Huntsman DG, Konishi I.
  • Journal Title: Cancer Res. Volume: 74 Issue: 22 Pages: 6519-6530
  • DOI: 10.1158/0008-5472.can-14-0847
  • Peer Reviewed / Open Access
• [Journal Article] 3.Menstrual cyclic change of metastin/GPR54 in endometrium. (2014)
  • Author(s): Baba T, Kang HS, Hosoe Y, Kharma B, Abiko K, Matsumura N, Hamanishi J, Yamaguchi K, Yoshioka Y, Koshiyama M, Mandai M, Murphy SK, Konishi I.
  • Journal Title: Med Mol Morphol Volume: 未定
  • Peer Reviewed
• [Journal Article] 【がん免疫療法の進歩】 Immune-checkpoint阻害によるがん免疫療法(解説/特集) (2014)
  • Author(s): 濱西 潤三*
  • Journal Title: 細胞 Volume: 46 Pages: 405-408
• [Journal Article] 難治性卵巣癌の克服を目指して 化学療法抵抗性卵巣癌の局所免疫の解析に基づいた、がん免疫逃避を標的とした新規治療戦略（第53回日本産科婦人科学会 学術集会 シンポジウム腫瘍） (2014)
  • Author(s): 濵西潤三*
  • Journal Title: 日本産科婦人科学会雑誌 Volume: 66 Pages: 2777-2791
• [Journal Article] 【がん免疫抑制・免疫疲弊と新規治療】 免疫チェックポイントPD-1/PD-L1経路を標的とする新しいがん治療(解説/特集) (2014)
  • Author(s): 濱西 潤三*, 小西 郁生
  • Journal Title: 癌と化学療法 Volume: 41 Pages: 1071-1076
• [Journal Article] 免疫学的視点から見た卵巣癌 (2014)
  • Author(s): 濱西 潤三*
  • Journal Title: 産婦人科の進歩 Volume: 66 Pages: 177-181
  • NAID: 130004438620
• [Journal Article] 卵巣癌のMolecular Medicine 遺伝子発現解析に基づく卵巣癌の薬剤選択を目指して(解説) (2014)
  • Author(s): 松村 謙臣, 村上 隆介, 山ノ井 康二, 山村 省吾, 山口 建, 濱西 潤三, 吉岡 弓子, 馬場 長, 森 誠一, 小西 郁生, 万代 昌紀
  • Journal Title: 日本婦人科腫瘍学会雑誌 Volume: 32 Pages: 203-210
• [Presentation] Use of Immunotherapy in platinum-resistant ovarian cancer (2016)
  • Author(s): Junzo Hamanshi
  • Organizer: Asian Oncology Summit 2016. AOS Session: Immunotherapy
  • Place of Presentation: ウエスティン都ホテル
  • Year and Date: 2016-03-03
  • Int'l Joint Research / Invited
• [Presentation] Evaluating the Potential of Immune Checkpoint Inhibitors in Ovarian Cancer (2015)
  • Author(s): Junzo Hamanshi
  • Organizer: ESMO Asia 2015. Expert Panel (Invited Oral)
  • Place of Presentation: Suntec City.Singapore
  • Year and Date: 2015-12-18
  • Int'l Joint Research / Invited
• [Presentation] Immunotherapy for gynecological cancers: Challenges and opportunities (2015)
  • Author(s): Junzo Hamanshi
  • Organizer: ESMO Asia 2015. Precision medicine and developmental therapeutics in gynaecologic oncology (Special Symposium)
  • Place of Presentation: Suntec City.Singapore
  • Year and Date: 2015-12-18
  • Int'l Joint Research / Invited
• [Presentation] Clinical impact of anti-PD-1 antibody (Nivolumab) for platinum-resistant ovarian cancer; Investigator initiated phase II clinical trial (2015)
  • Author(s): Hamanishi J, Mandai M, Matsumura N, Abiko K, Yamaguchi K, Baba T, Konishi I
  • Organizer: The 4th Biennial Meeting of Asian Society of Gynecologic Oncology (Oral presentation)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] 卵巣癌の微小免疫環境解析と抗PD-1抗体療法の展望 (2015)
  • Author(s): 濱西 潤三、万代 昌紀、松村 謙臣、安彦 郁、村上 隆介、馬場 長、山口 建、小西郁生
  • Organizer: 第53回日本癌治療学会学術集会 臓器別シンポジウム
  • Place of Presentation: 国立京都国際会議場
  • Year and Date: 2015-10-30
  • Invited
• [Presentation] Chemoimmunotherapy with PD-1 blockade and paclitaxel induce a potent antitumor immunity in ovarian cancers (2015)
  • Author(s): Hamanishi J, Peng J, Matsumura N. Abiko K, , Baba T, Yamaguchi K, Hosoe Y, Konishi I, Mandai M
  • Organizer: Advances in Ovarian Cancer Research: Exploiting Vulnerabilities
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Survival and Durable Tumor Remission for platinum-resistant Ovarian Cancer receiving Nivolumab (anti-PD-1 antibody). (2015)
  • Author(s): Hamanishi J, Mandai M, Matsumura N. Abiko K, Peng J, Horikawa N, Baba T, Yamaguchi K, Hosoe Y, Konishi I.
  • Organizer: The 74rd Annual Meeting of Japan Cancer Association, International Session
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] Efficacy and safety of anti-PD-1 antibody (Nivolumab: BMS-936558, ONO-4538) in patients with platinum-resistant ovarian cancer (2015)
  • Author(s): Junzo Hamanishi, Masaki Mandai*, Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, , Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Toshinori Murayama, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Satoshi Morita, Masayuki Yokode, Akira Shimizu, Tasuku Honjo, Ikuo Konishi
  • Organizer: The 50th Annual meeting of American Society of Clinical Oncology (ASCO) Clinical Science Symposium
  • Place of Presentation: Chicago USA.
  • Year and Date: 2015-06-01
• [Presentation] Durable Tumor Remission in Patients with Platinum-Resistant Ovarian Cancer Receiving Nivolumab (2015)
  • Author(s): Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Matsumura N, Abiko K, Baba T, Yamaguchi K, Ueda A, Hosoe Y, Morita S, Shimizu A, Honjo T, Konishi I.
  • Organizer: The 51th Annual meeting of American Society of Clinical Oncology (ASCO)
  • Place of Presentation: Chicago USA
  • Year and Date: 2015-05-30
  • Int'l Joint Research
• [Presentation] 「抗PD 1 抗体（Nivolumab）を用いた卵巣癌に対する第II 相医師主導治験」 (2015)
  • Author(s): 濵西潤三、万代昌紀、松村謙臣、安彦郁、馬場長、山口建、植田彰彦、小西郁生
  • Organizer: 第67回 日本産科婦人科学会学術集会 （優秀演題賞受賞講演）
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-04-10
  • Invited
• [Presentation] “<Scientific Plenary> Durable anti-tumor response of Nivolumab (anti-PD-1 antibody) for platinum-resistant ovarian cancer; phase II clinical trial” (2015)
  • Author(s): Hamanishi J, Mandai M, Matsumura N, Abiko K, Baba T, Yamaguchi K, Konishi I
  • Organizer: Annual Meeting on Woman’s Cancer.
  • Place of Presentation: Chicago
  • Year and Date: 2015-03-31
• [Presentation] 「文部科学省 橋渡し研究加速ネットワーク～抗PD-1抗体（Nivolumab）を用いたプラチナ抵抗性再発・進行卵巣癌に対する治療効果と安全性の評価～」 (2015)
  • Author(s): 濱西潤三、清水章, 池田隆文
  • Organizer: 文部科学省・厚生労働省 革新的医療技術創出拠点プロジェクト 「医療イノベーション創出ネットワークの現状と展望―新しいフェーズに入ったアカデミアのシーズ開発」平成26年度成果報告会
  • Place of Presentation: 東京 コンベンションセンター
  • Year and Date: 2015-03-05
• [Presentation] 「府民公開講座 京都府内の専門医によるがん診療の最前線 (2015)
  • Author(s): 濵西 潤三
  • Organizer: 府民公開講座
  • Place of Presentation: 京都府立医科大学図書館ホール
  • Year and Date: 2015-02-22
  • Invited
• [Presentation] 「抗PD-1抗体（Nivolumab）を用いたあたらしいがん治療」 (2015)
  • Author(s): 濵西 潤三
  • Organizer: The 10th Kyoto Hematology Forum 招待講演 ミニレクチャー
  • Place of Presentation: ウェスティン都ホテル京都
  • Year and Date: 2015-02-21
  • Invited
• [Presentation] 「卵巣癌に対する抗PD-1抗体を用いた医師主導第II相治験」 (2015)
  • Author(s): 濵西 潤三
  • Organizer: がんプロフェッショナル養成基盤推進プラン 第3回 トランスレーショナルリサーチシンポジウム「がん免疫療法の最前線」
  • Place of Presentation: 慶応義塾大学
  • Year and Date: 2015-02-14
  • Invited
• [Presentation] Immunotherapy with anti-PD-1 antibody (Nivolumab) is promising: Phase II trial for platinum-resistant ovarian cancer (2014)
  • Author(s): Junzo Hamanishi, Masaki Mandai, Noriomi Matsumura, Kaoru Abiko, Jin Peng, Naoki Horikawa, Kumuruz Murat, Tsukasa Baba, Ken Yamaguchi, Ikuo Konishi
  • Organizer: 第43回日本免疫学会学術集会 The 43rd JSI Workshop
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-12-11
• [Presentation] 免疫チェックポイントPD-1経路を標的とした 新しいがん治療 (2014)
  • Author(s): 濵西 潤三
  • Organizer: 第11回 がんワクチン療法研究会学術集会 特別講演
  • Place of Presentation: 東京女子医大
  • Year and Date: 2014-11-22
  • Invited
• [Presentation] A Phase II Clinical Trial of Immunotherapy with Anti-PD-1 Antibody (Nivolumab) in Advanced/Relapsed, Platinum-resistant Ovarian Cancer (2014)
  • Author(s): Junzo Hamanishi, Masaki Mandai, Noriomi Matsumura, Kaoru Abiko, Jin Peng, Naoki Horikawa, Tsukasa Baba, Ken Yamaguchi, Ikuo Konishi
  • Organizer: 15th Biennial Meeting of The International Gynecological Cancer Society
  • Place of Presentation: Melbourne Australia
  • Year and Date: 2014-11-08
• [Presentation] 市民公開講座『がんへの挑戦～京都大学の取組み～』世界が注目！ (2014)
  • Author(s): 濱西潤三
  • Organizer: 市民公開講座 京都大学臨床研究総合センター（iACT）
  • Place of Presentation: 京都大学
  • Year and Date: 2014-10-19
  • Invited
• [Presentation] Immune checkpoint PD-1 signal: the metastatic promotion of ovarian cancer and the target of new treatment strategy (2014)
  • Author(s): Junzo Hamanishi, Masaki Mandai, Noriomi Matsumura, Kaoru Abiko, Jin Peng, Naoki Horikawa, Tsukasa Baba, Ken Yamaguchi, Ikuo Konishi
  • Organizer: The 73rd JCA Symposia（第73回日本癌学会学術集会 シンポジウム）
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-27
• [Presentation] がん治療のパラダイムシフト ～抗PD-1抗体（Nivolumab）を用いた卵巣癌への挑戦～ (2014)
  • Author(s): 濵西潤三
  • Organizer: 平成26年度 一土会講演会 特別講演
  • Place of Presentation: ホテルアソシア静岡
  • Year and Date: 2014-09-03
  • Invited
• [Presentation] 抗PD-1抗体（Nivolumab）を用いた卵巣癌に対する第II相医師主導治験 (2014)
  • Author(s): 濵西潤三、万代昌紀、池田隆文、南 学、森由紀子、松本繁巳、竹馬俊介、村山 敏典、松村謙臣、安彦郁、山口建、植田彰彦、森田智視、清水章、本庶佑、小西郁生
  • Organizer: 第52回 日本癌治療学会学術集会 最優秀演題賞受賞講演
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-08-29
• [Presentation] 化学療法抵抗性卵巣癌の局所免疫の解析に基づいたがん免疫逃避を標的とした新規治療戦略 (2014)
  • Author(s): 濵西 潤三
  • Organizer: 第66回 日本産科婦人科学会学術講演会 シンポジウム：腫瘍 難治性卵巣癌の克服を目指して
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2014-04-19
• [Remarks] 京都大学医学部附属病院 産科婦人科
  • URL: http://www.kuhp.kyoto-u.ac.jp/~obgy/