Molecular Mechanisms of Nucleic Acid Receptors in Activating Innate Immune Respnses and Tumor Immunity.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07208
• 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: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: TANEGASHIMA Kosuke 公益財団法人東京都医学総合研究所, 基礎医科学研究分野, 主席研究員 (20507678)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: CpG DNA / CXCL14 / Innate Immunity / Tumor immunity / CpG ODN

Outline of Final Research Achievements

CpG ODN strongly activates Th1-type immune responses, which are essential for anti-tumor activity. Our research has revealed that CXC chemokines, exemplified by CXCL14, have a non-canonical function of delivering DNA into cells. CpG ODN is delivered to the intracellular CpG ODN receptor, TLR9, to activate anti-tumor immunity. However, receptors for the extracellular CpG ODN receptor have not been completely identified yet. In this study, we conducted expression cloning and isolated multiple candidate receptors for CpG ODN/CXCL14. Among these, we discovered that Igsf receptors spontaneously internalize without a ligand and play a crucial role in delivering CpG ODN to TLR9.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、CpG ODN/CXCL14複合体の受容体を解明した。CpG ODNによる腫瘍免疫誘導には効率の良い送達システムの構築が重要である。細胞外のCpG ODN受容体の分子実態が解明されたことでCpG ODNの送達を改善し、抗腫瘍効果を高める新たな分子機序の解明につながると考えられる。また、DNAのような普遍的な分子が免疫系の活性化に使われる際に、どの様な制御がなされているかを知る上でも学術的に意義深いと考える。