• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analysis of the immuno-genome and the effects of heavy ion therapy on mucosal melanoma of the nasal cavity and paranasal sinuses

Research Project

Project/Area Number 21K09625
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionChiba University

Principal Investigator

Hanazawa Toyoyuki  千葉大学, 大学院医学研究院, 教授 (90272327)

Co-Investigator(Kenkyū-buntansha) 猪爪 隆史  千葉大学, 大学院医学研究院, 教授 (80334853)
冨樫 庸介  千葉県がんセンター(研究所), がん治療開発グループ 細胞治療開発研究部, 客員研究員 (80758326)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords腫瘍免疫 / 粘膜型悪性黒色腫 / インターフェロンγ / 主要組織適合抗原複合体クラスI(MHC-I) / 重粒子線治療 / 悪性黒色腫 / 腫瘍浸潤リンパ球 / 免疫チェックポイント阻害薬 / 免疫ゲノム解析
Outline of Research at the Start

鼻副鼻腔を原発とする粘膜型悪性黒色腫は、手術と重粒子線治療を組み合わせることで、比較的良好な局所制御率を達成しているが、依然として遠隔転移が多く予後不良であり、より有効な治療が求められている。一方、悪性黒色腫に対する免疫チェックポイント阻害薬の効果が証明されたが、重粒子線などによる抗腫瘍免疫応答への影響は未だ明らかでない。重粒子線治療を受けた臨床検体ではPD-L1陽性率は上昇し、腫瘍微小環境への影響が示唆された。貴重な臨床検体と、樹立した患者由来悪性黒色腫細胞株とペアの腫瘍浸潤リンパ球により腫瘍微小環境を再現する系を用いて、重粒子線を含む放射線治療の抗腫瘍免疫応答への影響を明らかにする。

Outline of Final Research Achievements

Cancer cells are eliminated mainly by CD8+ T cells recognizing antigens presented on major histocompatibility complex class I (MHC-I). Since heavy ion therapy is reported to increase the MHC-I expression, we analyzed the signaling pathways involved in MHC-I expression. Although the IFNγ signaling pathway is essential for MHC-I expression in previous reports, some cancer cells have high MHC-I expression independently of the IFNγ signaling pathway. It has been generally thought that IFNγ signaling pathway defects result in resistance to immune checkpoint inhibitors (ICIs). However, ICIs exhibit efficacy against the high MHC-I-expressing tumors despite defects in IFNγ signaling pathways. Moreover, the CRISPR screening showed that the PI3K/Akt signaling pathway and its downstream NF-κB signaling pathway could increase MHC-I expression.

Academic Significance and Societal Importance of the Research Achievements

抗腫瘍免疫応答におけるMHC-Iの発現の重要性とそれに関わるシグナルについて詳細に検討したことで、MHC-Iを上昇させ得る重粒子線治療とICIの併用療法など、新規治療開発に繋がる可能性がある。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2021

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] High Expression of MHC Class I Overcomes Cancer Immunotherapy Resistance Due to IFNγ Signaling Pathway Defects2023

    • Author(s)
      Kawase K、Kawashima S、Nagasaki J、Inozume T、Tanji E、Kawazu M、Hanazawa T、Togashi Y
    • Journal Title

      Cancer Immunology Research

      Volume: In press Issue: 7 Pages: 895-908

    • DOI

      10.1158/2326-6066.cir-22-0815

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes2022

    • Author(s)
      Nagasaki Joji、Inozume Takashi、Yosuke Togashi et al.
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 5 Pages: 110331-110331

    • DOI

      10.1016/j.celrep.2022.110331

    • NAID

      120007192058

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ニボルマブを使用した再発・転移性頭頸部癌44例の検討2021

    • Author(s)
      川瀬勝隆、越塚慶一、米田理葉、山﨑一樹、米倉修二、花澤豊行
    • Journal Title

      頭頸部癌

      Volume: 47 Pages: 284-289

    • NAID

      130008114711

    • Related Report
      2021 Research-status Report
  • [Presentation] High major histocompatibility complex class I expression overcomes cancer immunotherapy resistance due to interferon gamma signaling pathway defects.2023

    • Author(s)
      Kawase K, Kawashima S, Nagasaki J, Inozume T, Yamamoto H, Kawazu M, Hanazawa T, Togashi Y.
    • Organizer
      AACR Annual Meeting 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Increasing MHC class I expression is crucial for antitumor immunity among IFNγ signaling pathways.2023

    • Author(s)
      Kawase K, Kawashima S, Nagasaki J, Inozume T, Kawazu M, Hanazawa T, Togashi Y.
    • Organizer
      第82回日本癌学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ニボルマブを使用した再発・転移性頭頸部癌44例の検討2021

    • Author(s)
      川瀬勝隆、越塚慶一、米田理葉、山﨑一樹、米倉修二、花澤豊行
    • Organizer
      第45回日本頭頸部癌学会
    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi