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Identification of molecules that mediate acquired resistance for anti-PD-1 therapy

Research Project

Project/Area Number 17K16335
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Dermatology
Research InstitutionUniversity of Yamanashi

Principal Investigator

Ohnuma Takehiro  山梨大学, 大学院総合研究部, 助教 (80793116)

Research Collaborator INOZUME takashi  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords抗PD-1抗体 / 治療抵抗性 / MHC class I消失 / 腫瘍浸潤リンパ球 / 免疫チェックポイント阻害剤 / メラノーマ / B2M / 再発 / TIL / 治療抵抗性因子
Outline of Final Research Achievements

Relapses long after the initial positive responses during anit-PD-1 therapy are sometimes observed. In this study, we compared two metastatic lesions. Both lesions initially regressed by anti-PD-1 therapy, and then one of them started to grow long after the initial response. In the shrinking lesion, there was no tumor cells. On the other hands, in the relapsed lesion tumor cells lost expression of MHC class I, an essential molecule to be recognized T cells completely, regardless of the preserved function of tumor specific T cells in the lesion.

Academic Significance and Societal Importance of the Research Achievements

抗PD-1抗体を用いて治療中のメラノーマ病巣内のがん特異的T細胞とがん細胞の状態を直接解析して明らかにした研究はまだ少ない。今回我々が得た知見は、免疫チェックポイント阻害剤を含むがん免疫療法の明らかな限界を示すと同時に、同様の研究をより多くの症例で実施することによって、抗PD-1抗体療法に本質的で臨床判断に役立つ有用なバイオマーカーをもたらす可能性を示した。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2019 2018 2017 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (2 results) Remarks (2 results)

  • [Journal Article] Analysis of the tumor reactivity of tumor-infiltrating lymphocytes in a metastatic melanoma lesion that lost MHC class I expression after anti-PD-1 therapy.2019

    • Author(s)
      Inozume T, Yaguchi T, Ariyasu R, Togashi Y, Ohnuma T, Honobe A, Nishikawa H, Kawakami Y, Kawamura T.
    • Journal Title

      J Invest Dermatol.

      Volume: 印刷中 Issue: 7 Pages: 30023-5

    • DOI

      10.1016/j.jid.2019.01.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Case of metastatic uveal melanoma in which an antitumor effect appeared after ipilimumab discontinuation due to autoimmune hypophysitis2017

    • Author(s)
      Ohnuma Takehiro, Takashi Inozume et al
    • Journal Title

      Journal of Dermatology

      Volume: 44 Issue: 11 Pages: 1325-1326

    • DOI

      10.1111/1346-8138.13692

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 抗PD-1抗体により長期安定後に悪化した病巣のメラノーマ細胞とTILの解析2018

    • Author(s)
      猪爪隆史、谷口智憲、大沼毅紘、河上裕、川村龍吉
    • Organizer
      第22回日本がん免疫学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] イピリムマブ投与後に生じた自己免疫性下垂体炎の1例2017

    • Author(s)
      大沼毅紘、猪爪隆史ら
    • Organizer
      第69回日本皮膚科学会西部支部学術大会
    • Related Report
      2017 Research-status Report
  • [Remarks] 山梨大 皮膚科 ホームページ 研究グループ紹介

    • URL

      https://www.med.yamanashi.ac.jp/clinical/dermatol/groupe/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] ノーベル賞のがん免疫薬、効力向上へ 進む研究

    • URL

      https://www.nikkei.com/article/DGXMZO36186080V01C18A0TJM000/

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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