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

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21328
• Project/Area Number (Other): 18H06228 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0903:Organ-based internal medicine and related fields
• Research Institution: Kumamoto 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
• 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

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 We found that a tumor-derived factor X (unpublished) can suppress the expression of type I IFN-inducible genes and of IL-12 p40 in mouse bone marrow-derived DCs. Additionally, we found that X can induce the expression of gene Y, a transcription factor (unpublished), in DCs.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.

Free Research Field

皮膚科学

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。