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

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09625
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Chiba 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
• 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

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.

Free Research Field

腫瘍免疫

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。