Analysis of cancer immune evasion through induction of steroid like agent, GITRL against NK cells

• Project/Area Number: 25861156
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Hiroshima University
• Principal Investigator: OHIRA MASAHIRO 広島大学, 大学病院, 病院助教 (30397947)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ＮＫ細胞 / 癌免疫 / ステロイド / NK細胞 / 肝細胞癌 / 自然免疫 / GITRL

Outline of Final Research Achievements

Cancer might alter microenvironment to enable immune escape. To investigate how HCC got immune evasion through GITRL in human HCC, we analyzed the phenotype of liver NK cells and effect of GITRL on NK cells. GITRL released from HCC were shown to suppress NK cell activity in vitro. Liver NK cells expressed more GITRL receptor, GITR than peripheral blood NK cells did. Interestingly, HCC patients had very low level of GITR expression on liver NK cells. Exposure to inflammatory cytokine upregulated GITR expression on liver NK cells. These findings suggest that the effect of GITRL on NK cells might manipulate microenvironment for cancer cells to evade immune system.