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Immune evasion mechanism of tumors mediated by NK cell receptors

Research Project

Project/Area Number 19K22556
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionKanazawa University

Principal Investigator

Hirayasu Kouyuki  金沢大学, 先進予防医学研究センター, 特任准教授 (30585170)

Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords免疫逃避機構 / 腫瘍細胞 / NK細胞 / NK細胞レセプター / NK細胞 / NK細胞レセプター
Outline of Research at the Start

NK細胞は、腫瘍細胞に対して殺傷能力を示すことが従来から知られているが、分子標的に基づいたがん免疫療法の開発には至っていない。これは、NK細胞の抑制化レセプターの役割が十分に理解されていないことが原因の一つである。そこで本研究では、最近申請者らが見出した腫瘍細胞を認識する抑制性NK細胞レセプターに着目し、腫瘍の免疫逃避機構の解明を行うことで、新たながん免疫療法の標的分子の開拓につなげることを目的とする。

Outline of Final Research Achievements

This study aims to elucidate the immune evasion mechanism of tumors focused on the inhibitory NK cell receptor KIRs, leading to the development of new target molecules for cancer immunotherapy.
A comprehensive analysis of the interaction between various inhibitory KIRs and various tumor cells revealed that one of the KIRs recognizes specific tumor cells, in which this study identified the candidate ligand. These results suggest that certain tumor cells may utilize the KIR ligands for immune evasion.

Academic Significance and Societal Importance of the Research Achievements

がん患者では、免疫ががん細胞を排除できず免疫抑制状態となっていることが分かってきているが、その分子メカニズムは十分明らかとなっていない。本研究により、Natural Killer (NK)細胞に発現する免疫抑制化レセプターが特定のがん細胞を認識して免疫を抑制する可能性が示唆された。今後さらにこの免疫抑制化レセプターの抑制機能が明らかになれば、がん免疫療法の新たな標的分子につながることが期待できる。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (8 results)

All 2021 2020 2019

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

  • [Journal Article] Characterization of LILRB3 and LILRA6 allelic variants in the Japanese population2021

    • Author(s)
      Hirayasu K, Sun J, Hasegawa G, Hashikawa Y, Hosomichi K, Tajima A, Tokunaga K, Ohashi J, Hanayama R.
    • Journal Title

      Journal of Human Genetics

      Volume: 印刷中 Issue: 7 Pages: 739-748

    • DOI

      10.1038/s10038-021-00906-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasmodium falciparum RIFIN is a novel ligand for inhibitory immune receptor LILRB2.2021

    • Author(s)
      Sakoguchi A, Saito F, Hirayasu K, Shida K, Matsuoka S, Itagaki S, Nakai W, Kohyama M, Suenaga T, Iwanaga S, Horii T, Arase H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 548 Pages: 167-173

    • DOI

      10.1016/j.bbrc.2021.02.033

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular mechanism of the recognition of bacterially cleaved immunoglobulin by the immune regulatory receptor LILRA22020

    • Author(s)
      Yamazaki Rika、Furukawa Atsushi、Hirayasu Kouyuki、Yumoto Kohei、Fukuhara Hideo、Arase Hisashi、Maenaka Katsumi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 28 Pages: 9531-9541

    • DOI

      10.1074/jbc.ra120.013354

    • NAID

      120007116484

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genotype and phenotype analysis of patients with pediatric cutaneous mastocytosis, especially wild‐type KIT patients2020

    • Author(s)
      Arase Noriko、Wataya‐Kaneda Mari、Murota Hiroyuki、Nakagawa Yukinobu、Yamaoka Toshifumi、Itoi‐Ochi Saori、Hirayasu Kouyuki、Arase Hisashi、Fujimoto Manabu、Katayama Ichiro
    • Journal Title

      The Journal of Dermatology

      Volume: 47 Issue: 4 Pages: 426-429

    • DOI

      10.1111/1346-8138.15266

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Genetic and functional diversity of leukocyte immunoglobulin-like receptor family in humans2021

    • Author(s)
      Hirayasu Kouyuki
    • Organizer
      3rd Japan-Germany Symposium on Advanced Preventive Medicine 2021
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] LILRファミリーにみる遺伝的・機能的多様性2020

    • Author(s)
      平安恒幸
    • Organizer
      日本人類遺伝学会第65回大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Characterization of allelic and functional variations of LILRB3 and LILRA6 in the Japanese population.2020

    • Author(s)
      Sun J, Hirayasu K, Hanayama R.
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 免疫逃避機構からみた宿主と微生物の相互作用2019

    • Author(s)
      平安 恒幸
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-07-04   Modified: 2022-01-27  

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