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Identification of chemokine-network causing MDSC migration in ovarian cancer microenvironment

Research Project

Project/Area Number 20K16431
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kyoto Medical Center

Principal Investigator

Abiko Kaoru  独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究員 (20508246)

Project Period (FY) 2020-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords卵巣癌 / 子宮体癌 / ケモカイン / 子宮頸癌 / 腫瘍免疫 / MDSC / マクロファージ / 免疫治療 / 遊走
Outline of Research at the Start

本研究では、患者の血清および腫瘍サンプルから、MDSCの量やサブタイプ、表面ケモカイン受容体発現、血清中のケモカインの濃度を多数例で解析することにより、卵巣癌のMDSC浸潤と関連するケモカインネットワークを明らかにする。最終的には、どのケモカインを治療標的とするかを選択するための血清ケモカインパネルを作成するための基礎データを得ることを目的とする。

Outline of Final Research Achievements

CXCL1 and CXCL2 concentrations in pretreatment serum of patients with ovarian cancer (including fallopian tube and peritoneal cancer), uterine body cancer, and cervical cancer were measured by ELISA. Both factors were high in uterine and ovarian cancers, and especially CXCL1 and CXCL2 showed a strong correlation. CXCL2 correlated with LDH and CXCL1/2 with neutrophil/lymphocyte ratio, but not with CRP or white blood cell count. CXCL1/2 was not correlated with stage of clinical progression or age, but CXCL1/2 was very high in patients who relapsed or died of their primary disease. These results suggest that CXCL1 and CXCL2 reflect immune status and prognosis in ovarian and uterine cancer and may be universal prognostic markers independent of histological type.

Academic Significance and Societal Importance of the Research Achievements

婦人科癌の中でも、卵巣癌と子宮体癌は増え続けている。免疫チェックポイント阻害薬が効果を示す症例では長期の治療効果が得られることもあるが、卵巣癌の多くと子宮体癌の一部には免疫チェックポイントの効果が乏しい。我々は免疫抑制性細胞とそれらを遊走(癌の近くに集める)サイトカイン・ケモカインが免疫チェックポイント阻害薬の効果を減弱させていることを治療前血清中のCXCL1およびCXCL2を測定し、種々の免疫マーカーとの関連を示した。

Report

(6 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (19 results)

All 2025 2024 2023 2022 2021 2020

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 11 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Differentiation of uterine fibroids and sarcomas by MRI and serum LDH levels: a multicenter study of the KAMOGAWA study2025

    • Author(s)
      Yamanishi Yukio、Kotani Yasushi、Kido Aki、Otani Tomoyuki、Himoto Yuki、Kurata Yasuhisa、Murakami Kosuke、Takaya Hisamitsu、Sumitomo Masahiro、Emoto Ikuko、Matsubara Motonori、Horikawa Naoki、Akagi Kana、Ishida Kentaro、Takaori Aya、Sakurai Azusa、Abiko Kaoru、Yamanoi Koji、Mandai Masaki、Matsumura Noriomi
    • Journal Title

      Journal of Gynecologic Oncology

      Volume: 36 Issue: 4

    • DOI

      10.3802/jgo.2025.36.e58

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FSH-producing pituitary neuroendocrine tumor as a cause of ovarian hyperstimulation syndrome2024

    • Author(s)
      Kitamura Takuya、Nanba Kazutaka、Doi Kento、Kishimoto Naoya、Abiko Kaoru、Kuwahara Ryo、Moriyoshi Koki、Inoshita Naoko、Tagami Tetsuya
    • Journal Title

      Endocrinology, Diabetes & Metabolism Case Reports

      Volume: 2024 Issue: 1 Pages: 0119-0119

    • DOI

      10.1530/edm-23-0119

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SLFN11 is a <i>BRCA</i> Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma2023

    • Author(s)
      Akashi Hidehiko、Yachida Nozomi、Ueda Haruka、Yamaguchi Manako、Yamawaki Kaoru、Tamura Ryo、Suda Kazuaki、Ishiguro Tatsuya、Adachi Sosuke、Nagase Yoshikazu、Ueda Yutaka、Ueda Masashi、Abiko Kaoru、Kagabu Masahiro、Baba Tsukasa、Nakaoka Hirofumi、Enomoto Takayuki、Murai Junko、Yoshihara Kosuke
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 23 Issue: 1 Pages: 106-116

    • DOI

      10.1158/1535-7163.mct-23-0257

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Treatment With Antitumor Agents Recommended by Cancer Genome Panel for Uterine Leiomyosarcoma2023

    • Author(s)
      Hayashi Takuma、Kishimoto Naoya、Abiko Kaoru、Konishi Ikuo
    • Journal Title

      Journal of Clinical Medicine Research

      Volume: 15 Issue: 10-11 Pages: 461-468

    • DOI

      10.14740/jocmr5052

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristic of Endometrial Stromal Sarcoma by Algorithm of Potential Biomarkers for Uterine Mesenchymal Tumor2023

    • Author(s)
      Hayashi Takuma、Sano Kenji、Yaegashi Nobuo、Abiko Kaoru、Konishi Ikuo
    • Journal Title

      Current Issues in Molecular Biology

      Volume: 45 Issue: 8 Pages: 6190-6201

    • DOI

      10.3390/cimb45080390

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics2022

    • Author(s)
      Konishi I, Abiko K, Hayashi T, Yamanoi K, Murakami R, Yamaguchi K, Hamanishi J, Baba T, Matsumura N, Mandai M; Kyoto Study Group for Ovarian Cancer Research.
    • Journal Title

      J Gynecol Oncol

      Volume: 33(5) Issue: 5

    • DOI

      10.3802/jgo.2022.33.e83

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic host immunity and PD-L1/PD-1 blockade efficacy: developments after “IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer”2022

    • Author(s)
      Abiko Kaoru、Hamanishi Junzo、Matsumura Noriomi、Mandai Masaki
    • Journal Title

      British Journal of Cancer

      Volume: 128 Issue: 3 Pages: 461-467

    • DOI

      10.1038/s41416-022-01960-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] CXCL13-producing CD4+ T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer2022

    • Author(s)
      Ukita Masayo、Hamanishi Junzo、Yoshitomi Hiroyuki、Yamanoi Koji、Takamatsu Shiro、Ueda Akihiko、Suzuki Haruka、Hosoe Yuko、Furutake Yoko、Taki Mana、Abiko Kaoru、Yamaguchi Ken、Nakai Hidekatsu、Baba Tsukasa、Matsumura Noriomi、Yoshizawa Akihiko、Ueno Hideki、Mandai Masaki
    • Journal Title

      JCI Insight

      Volume: 7 Issue: 12 Pages: 157215-157215

    • DOI

      10.1172/jci.insight.157215

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunosuppressive tumor microenvironment in Uterine Serous Carcinoma via CCL7 signal with myeloid-derived suppressor cells.2022

    • Author(s)
      Mise Y, Hamanishi J, Daikoku T, Takamatsu S, Miyamoto T, Taki M, Yamanoi K, Yamaguchi K, Ukita M, Horikawa N, Abiko K, Murakami R, Furutake Y, Hosoe Y, Terakawa J, Kagabu M, Sugai T, Osakabe M, Fujiwara H, Matsumura N, Mandai M, Baba T.
    • Journal Title

      Carcinogenesis

      Volume: na Issue: 7 Pages: 647-658

    • DOI

      10.1093/carcin/bgac032

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] B7-H3 Suppresses Antitumor Immunity via the CCL2-CCR2-M2 Macrophage Axis and Contributes to Ovarian Cancer Progression2022

    • Author(s)
      Miyamoto T, Murakami R, Hamanishi J, Tanigaki K, Hosoe Y, Mise N, Takamatsu S, Mise Y, Ukita M, Taki M, Yamanoi K, Horikawa N, Abiko K, Yamaguchi K, Baba T, Matsumura N, Mandai M.
    • Journal Title

      Cancer Immunol Res .

      Volume: 10 Issue: 1 Pages: 56-69

    • DOI

      10.1158/2326-6066.cir-21-0407

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tertiary lymphoid structures are associated with favorable survival outcomes in patients with endometrial cancer2021

    • Author(s)
      Qin Meng、Hamanishi Junzo、Ukita Masayo、Yamanoi Koji、Takamatsu Shiro、Abiko Kaoru、Murakami Ryusuke、Miyamoto Taito、Suzuki Haruka、Ueda Akihiko、Hosoe Yuko、Horie Akihito、Yamaguchi Ken、Mandai Masaki
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: online Issue: 6 Pages: 1431-1442

    • DOI

      10.1007/s00262-021-03093-1

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor Immune Microenvironment during Epithelial-Mesenchymal Transition.2021

    • Author(s)
      Taki M, Abiko K, Ukita M, Murakami R, Yamanoi K, Yamaguchi K, Hamanishi J, Baba T, Matsumura N, Mandai M.
    • Journal Title

      Clin Cancer Res

      Volume: - Issue: 17 Pages: 4459-4459

    • DOI

      10.1158/1078-0432.ccr-20-4459

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential Novel Ovarian Cancer Treatment Targeting Myeloid-Derived Suppressor Cells.2021

    • Author(s)
      Abiko K, Hayashi T, Yamaguchi K, Mandai M, Konishi I.
    • Journal Title

      Cancer Invest.

      Volume: 39(4) Pages: 310-314

    • DOI

      10.1080/07357907.2020.1871487

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cure after remission of recurrent ovarian cancer; a multicenter retrospective study.2024

    • Author(s)
      Matsumura N, Sumitomo M, Abiko K
    • Organizer
      ASGO2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 免疫チェックポイント阻害薬時代の子宮頸がん治療~手術、放射線、薬物療法から私たちは何を選べばよいのか~2024

    • Author(s)
      安彦郁
    • Organizer
      子宮頸がん治療セミナー
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] 免疫チェックポイント阻害薬時代の子宮頸がん治療~治療効果判定と副作用マネジメントを中心に~2023

    • Author(s)
      安彦郁
    • Organizer
      Cervical Cancer Seminar in Hokuriku, 2023年4月、金沢
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] 免疫チェックポイント阻害薬時代の子宮頸癌治療~治療効果判定と副作用マネジメントを中心に~」2023

    • Author(s)
      安彦 郁
    • Organizer
      Cervical Cancer Seminar in Hokuriku
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 卵巣癌の抗VEGF抗体獲得耐性の免疫学的機序の解明と克服2021

    • Author(s)
      安彦 郁
    • Organizer
      第62回日本婦人科腫瘍学会学術講演会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] シンポジウム1 腫瘍 免疫チェックポイント阻害薬の次へ~骨髄由来免疫抑制性細胞(MDSC)を標的とした卵巣がん新規治療の開発2020

    • Author(s)
      安彦 郁
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2026-01-16  

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