Enhanced Cancer Immunotherapy Using STAT3-Depleted Dendritic Cells with High Th1-Inducing Ability and Resistance to Cancer Cell-Derived Inhibitory Factors

摘要: STAT3 signaling constitutes an important negative feedback mechanism for the maintenance of immune homeostasis, a suppressive signal Th1 response in murine macrophages, and cancer evasion various cells. The strategy inhibition should be considered, because these features could impede effective immunotherapy. We have evaluated effects inactivation dendritic cells (DCs) on responses mice humans. DCs derived from LysMcre/STAT3flox/flox displayed higher cytokine production to TLR stimulation, activated T more efficiently, were resistant suppression by cancer-derived immunosuppressive factors compared with control littermates. Antitumor activities STAT3-depleted intratumoral administration gp70 Ag peptide-pulsed therapeutic MC38 tumor model. Intratumoral significantly inhibited growth both injected nontreated remote tumors. was accompanied increase gp70-specific cell as well systemic response. human adenoviral short hairpin RNA also capable producing cytokines stimulation factors, they induced Ag-specific efficiently than DCs. identified role DC vivo models vitro-specific induction humans indicates that STAT3-inactivated may promising approach