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Analyses and applications of type I interferon-inducible genes in skin disorders

Research Project

Project/Area Number 19K21328
Project/Area Number (Other) 18H06228 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 0903:Organ-based internal medicine and related fields
Research InstitutionKumamoto University

Principal Investigator

Kanemaru Hisashi  熊本大学, 病院, 病院教員 (20823313)

Project Period (FY) 2018-08-24 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsインターフェロン / 悪性黒色腫 / 代謝 / 腫瘍免疫 / 転写因子 / 樹状細胞 / サイトカイン / 免疫療法 / I型インターフェロン / 遺伝子 / 皮膚悪性腫瘍 / 免疫チェックポイント阻害薬 / 自然免疫
Outline of Research at the Start

近年、皮膚悪性腫瘍の一つである悪性黒色腫に対し、免疫チェックポイント阻害薬に代表される免疫療法の有効性が報告され、これらの治療成績に影響を与える重要な因子としてI型インターフェロン(IFN)が注目されている。本研究は皮膚免疫においてI型IFN誘導性遺伝子に重要な影響を与える因子を探索し、その病態における機序を解明することで、診断・予後マーカーとしての可能性を探り、さらに上記の免疫療法への応用の可能性を検討する。

Outline of Final Research Achievements

Malignant melanoma (MM) is an aggressive and potentially fatal neoplasm, for which effective treatments need to be developed urgently. Some reports suggest that type I interferons (IFNs), secreted by dendritic cells (DCs), could be involved in the therapeutic effectiveness of immune checkpoint blockers. From this perspective, we hypothesized that type I IFN-inducible genes may also be involved in tumor immunity. We found that a tumor-derived factor X (unpublished) can suppress the expression of type I IFN-inducible genes and of IL-12 p40 in mouse bone marrow-derived DCs. Additionally, we found that X can induce the expression of gene Y, a transcription factor (unpublished), in DCs. There was a significant increase in Y expression ratios in the primary tissues of patients with invasive MM as compared with the tumor tissues of MM in situ. These data suggest that factor X and gene Y may prove to be useful targets for treatment of MM with immune checkpoint blockers.

Academic Significance and Societal Importance of the Research Achievements

本研究は、I型インターフェロン誘導遺伝子および腫瘍由来の代謝産物の役割に関しその機序を解明することで、診断・予後マーカーとしての可能性を探り、免疫チェックポイント阻害薬(ICI)の奏効率改善も含めた治療応用についての可能性を検討することを目的としている。本研究は皮膚悪性腫瘍に対する治療成績の向上、および診断・予後予測精度の向上により、ICIの奏効率改善だけではなく、ICIに関連するコストの圧縮やさらに同様の手法を他の悪性腫瘍に展開できる可能性があるという側面もあり、学術的・社会的な意義を有している。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • Research Products

    (15 results)

All 2020 2019 2018

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (7 results)

  • [Journal Article] Successful treatment of occult pancreatic melanoma using BRAF/MEK inhibitors.2020

    • Author(s)
      Mizukami Y, Kanemaru H, Nakamura K, Hashigo S, Kajihara I, Miyashita A, Aoi J, Fukushima S, Honda Y, Ihn H.
    • Journal Title

      J Dermatol.

      Volume: 47 Issue: 4

    • DOI

      10.1111/1346-8138.15198

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of Endoglin Exerts Antitumor Effects through the Regulation of Non-Smad TGF-β Signaling in Angiosarcoma2020

    • Author(s)
      Ryoko Sakamoto, Ikko Kajihara, Hitomi Miyauchi, Saki Maeda-Otsuka, Saori Yamada-Kanazawa, Soichiro Sawamura, Hisashi Kanemaru, Katsunari Makino, Jun Aoi, Takamitsu Makino, Satoshi Fukushima, Mamiko Masuzawa, Mikio Masuzawa, Yasuyuki Amoh, Daichi Hoshina, Riichiro Abe, Hironobu Ihn
    • Journal Title

      Journal of Investigative Dermatology

      Volume: - Issue: 10 Pages: 2060-2072.e6

    • DOI

      10.1016/j.jid.2020.01.031

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serious disseminated intravascular coagulation associated with combination therapy of nivolumab and ipilimumab in advanced melanoma.2020

    • Author(s)
      Kuriyama H, Fukushima S, Nakahara S, Kanemaru H, Miyashita A, Aoi J, Tomita Y, Kawasaki T, Nosaka K, Ihn H.
    • Journal Title

      J Dermatol.

      Volume: - Issue: 6

    • DOI

      10.1111/1346-8138.15336

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induced pluripotent stem cell‐derived myeloid cells expressing OX40 ligand amplify antigen‐specific T cells in advanced melanoma2020

    • Author(s)
      Kimura Toshihiro、Fukushima Satoshi、Okada Etsuko、Miyashita Azusa、Tsukamoto Hirotake、Uemura Yasushi、Senju Satoru、Ihn Hironobu
    • Journal Title

      Pigment Cell & Melanoma Research

      Volume: - Issue: 5 Pages: 744-755

    • DOI

      10.1111/pcmr.12887

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful prednisolone treatment of peripartum Behçet’s disease associated with HLA-A262020

    • Author(s)
      Saori Kiyohara, Hisashi Kanemaru (corresponding author), Takehisa Suzuki, Kayo Nakamura, Noritoshi Honda, Katsunari Makino, Ikko Kajihara, Takamitsu Makino, Takashi Ohba, Hironobu Ihn
    • Journal Title

      Australasian Journal of Dermatology

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain abscess in an angiosarcoma patient during a disease-free interval2019

    • Author(s)
      Kuriyama H, Kajihara I, Kanemaru H, Nishimura Y, Igata T, Masuguchi S, Imaoka Y, Makino K, Ihn H
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 13 Issue: 3 Pages: 175-176

    • DOI

      10.5582/ddt.2019.01042

    • NAID

      130007682075

    • ISSN
      1881-7831, 1881-784X
    • Year and Date
      2019-06-30
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Case of cutaneous myoepithelioma managed with surgical resection without recurrence for 4?years.2019

    • Author(s)
      Kanemaru H, Honda N, Kubo Y, Nishihara H, Onuma T, Sakai K, Fukushima S, Inoue Y, Honda Y, Ihn H
    • Journal Title

      The Journal of dermatology

      Volume: 印刷中 Issue: 6

    • DOI

      10.1111/1346-8138.14769

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] he Warburg effect and tumour immune microenvironment in extramammary Paget's disease: overexpression of lactate dehydrogenase A correlates with immune resistance.2019

    • Author(s)
      Urata K, Kajihara I, Miyauchi H, Mijiddorj T, Otsuka-Maeda S, Sakamoto R, Sawamura S, Kanemaru H, Kanazawa-Yamada S, Makino K, Aoi J, Makino T, Fukushima S, Komohara Y, Ihn H.
    • Journal Title

      J Eur Acad Dermatol Venereol.

      Volume: - Issue: 8 Pages: 1715-1721

    • DOI

      10.1111/jdv.16145

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] The antitumor effect of BATF2 through IL-12 p40 up-regulation in tumor-associated macrophages2020

    • Author(s)
      金丸 央
    • Organizer
      日本研究皮膚科学会 第11回きさらぎ塾
    • Related Report
      2019 Annual Research Report
  • [Presentation] 悪性黒色腫の患者における血漿cfDNAを用いたBRAF遺伝子変異の検出2020

    • Author(s)
      金丸央、梶原一亨、宮内仁美、宮下梓、青井淳、福島聡、尹浩信
    • Organizer
      第119回日本皮膚科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腫瘍免疫における転写因子BATF2のIL-12p40発現促進の機序について2019

    • Author(s)
      金丸 央、佐藤 荘、福島 聡、尹 浩信、審良 静男
    • Organizer
      第35回日本皮膚悪性腫瘍学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 皮膚科疾患における転写因子BATFファミリーの意義とその応用2019

    • Author(s)
      金丸 央、佐藤 荘、福島 聡、尹 浩信、審良 静男
    • Organizer
      第118回日本皮膚科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 転写因子BATF2のIL-12p40発現促進機構2019

    • Author(s)
      金丸 央、佐藤 荘、福島 聡、尹 浩信、審良 静男
    • Organizer
      第23回日本がん免疫学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腫瘍関連マクロファージにおける転写因子BATF2のIL-12p40発現促進による抗腫瘍効果2018

    • Author(s)
      金丸 央、佐藤 荘、福島 聡、尹 浩信、審良 静男
    • Organizer
      第22回日本がん免疫学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 転写因子BATF2のIL-12p40発現促進による抗腫瘍効果について2018

    • Author(s)
      金丸 央、佐藤 荘、福島 聡、尹 浩信、審良 静男
    • Organizer
      第34回日本皮膚悪性腫瘍学会学術大会
    • Related Report
      2018 Annual Research Report

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Published: 2018-08-27   Modified: 2024-03-26  

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