Induction of liver-specific intrahepatic myeloid cells aggregation expands CD8 T cell and inhibits growth of murine hepatoma

ABSTRACTToll-Like Receptor 9 (TLR9) stimulation selectively triggers the formation of a cell cluster termed intrahepatic myeloid aggregation for T cell expansion” (iMATE) in a mouse chronic viral hepatitis model. iMATE expands cytotoxic T cells and controls viral hepatitis infection. The liver-specific immune response prompted this investigation of whether the effect could control tumor growth in the murine hepatic tumor model. Murine hepatic BNL cells were used to establish an orthotropic liver tumor model. We found that intravenous infusion of TLR 9 agonist, CpG oligodeoxynucleotide (ODN) induced iMATE formation in non-tumor parts of liver and suppressed the murine BNL tumor growth. The ratio of intra-tumor CD8+ T cells have increased after CpG ODN. These cells expressed higher levels of effector and checkpoint molecules, and produce more Th1 cytokine upon ex vivo stimulation. The CD11b+Ly6ChiLy6G – subset of CD11b+ myeloid cells in the tumor microenvironment has increased. Both CD11b+Ly6ChiLy6G – and C...