Mecanisms of cooperation between CXCL14 and DNA for activation of innate immune responces and tumor immunity

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07313
• 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): 2018-04-01 – 2021-03-31
• Keywords: CXCL14 / CpG DNA / tumor immunity / innate immunity / TLR9

Outline of Final Research Achievements

CpG DNA, a ligand for Toll-like Receptor (TLR) 9, strongly activates the Th1-type immune response, which is essential for antitumor immune response. We have shown that CXCL14 enhanced uptake of CpG DNA into dendritic cells by direct binding of CpG DNA. In this study, we analyzed the molecular mechanism of delivery of CpG DNA by CXCL14 and its role in tumor immunity. In CXCL14 knockout mice, the antitumor effect of CpG DNA was canceled, suggesting that CXCL14 is essential for the antitumor effect of CpG DNA in vivo. In addition, we showed that the binding ability of CXC chemokines to CpG DNA and the binding to uptake receptors may play important roles in the induction of antitumor immunity.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、CXCL14とCpG DNA複合体が腫瘍免疫を生体内でも活性化していることを見出した。CpG DNAを用いた腫瘍免疫誘導には効率の良い送達システムの構築が必要である。本研究で、CXCL14の関与とそのCpG DNA細胞内送達の分子メカニズムが解明されたことで、その開発に貢献できると考える。本研究で得られた成果は、免疫チェックポイント阻害剤を用いた治療に抵抗性の患者群のうち、樹状細胞の活性化が不十分な場合への治療に繋がる成果が期待できるほか、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、どのような制御が行われているかを知る上でも学術的に意義深いと考える。