Inactivation of IFN-induced chemokines by DPP4 and its clinical significance in oral cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K10102
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Meikai University
• Principal Investigator: MORI Kazumasa 明海大学, 歯学部, 准教授 (80372902)
• Co-Investigator(Kenkyū-buntansha): 廣井 美紀 明海大学, 歯学部, 准教授 (30419717) ; 大森 喜弘 明海大学, 歯学部, 教授 (50194311)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: DPP4 / 口腔扁平上皮癌 / CXCL10 / IFN誘導生ケモカイン / T細胞

Outline of Final Research Achievements

Stable expression cell lines of IFN-inducible chemokines CXCL9, CXCL10, and CXCL11 were constructed, and the following results were obtained regarding their antitumor effects. (1) CXCL9- and CXCL11-expressing cells inhibited tumor growth, but CXCL10 did not show any inhibitory effect. 2) Tumor tissues expressing CXCL9 and CXCL11 showed increased expression of NK1.1 and decreased expression of VEGF. 3) Tumor tissues expressing CXCL10 showed increased expression of DPP4, a chemokine cleaving enzyme. These results suggest that the anti-tumor effects of IFN-inducible chemokines, CXCL9, CXCL10, and CXCL11, are different and depend on the expression of DPP4, which cleaves chemokines, and the sensitivity of chemokines to this enzyme.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

IFN誘導性ケモカインCXCL10の腫瘍増殖能の要因を検討した．結果，CXCL10発現腫瘍組織は，ケモカインを切断する酵素DPP4の発現が多く認められた．これは DPP4によって切断された短縮型CXCL10が，癌関連線維芽細胞（CAFs）の動員あるいは分化に関与している可能性を考えた.現在癌治療に用いられる免疫チェックポイント阻害剤による免疫療法の有効性は, 腫瘍組織への細胞傷害性T細胞（CTL）の動員が必要であり, その動員にはIFN誘導性ケモカインが重要で，本研究で得られた知見は, DPP4を標的とした新たな免疫療法の奏功性改善の分子基盤の理解に貢献するものと考えている.