Roles of tumor-derived mitochondrial DAMPs in anti-rumor immunity and application to cancer immunotherapy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07668
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kurume University
• Principal Investigator: Waki Kayoko 久留米大学, 付置研究所, 講師 (40649597)
• Co-Investigator(Kenkyū-buntansha): 山田 亮 久留米大学, 付置研究所, 特命教授 (50158177)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ミトコンドリアDAMPs / ホルミルペプチド

Outline of Final Research Achievements

Mitochondrial N-formyl peptides (mtFPs) act as DAMPs (damage-associated molecular patterns) and are known to induce inflammation reactions. Inflammation in tumors has been reported to have inhibitory effects on anti-tumor immunity. We knocked out mitochondrial methionyl-tRNA formyltransferase (mtfmt), which catalyzes the formylation of methionyl-tRNA, in mouse tumor cell lines. When transplanted subcutaneously, the Mtfmt knockout (KO) clones grew slower in C57BL/6 mice. In addition, less immunosuppressive cells, such as myeloid-derived suppressor cells and regulatory T cells, were observed in Mtfmt KO tumors than in wild-type tumors, by immunohistochemistry and FACS analyses. These results suggested the possibility that mtFPs changed tumor microenvironment and affected negatively on anti-tumor immunity.

Free Research Field

がん免疫

Academic Significance and Societal Importance of the Research Achievements

腫瘍細胞から放出されるミトコンドリアDAMPsであるFPの抗腫瘍免疫における役割は明確ではなかった。本研究では、腫瘍ミトコンドリアFPを抑制すると、腫瘍増殖の抑制が見られた。更に、腫瘍内への抗腫瘍免疫を促進する免疫細胞の浸潤増加と、抑制性免疫細胞の浸潤減少も確認された。これらのことは、腫瘍ミトコンドリアFPを制御することで腫瘍微小環境を変化させ、抗腫瘍免疫が誘導・増強されたことを示唆し、他のがん治療法と併用する次世代複合免疫療法の開発の可能性を示唆している。