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• W2016268206 abstract "PolyI:C is a nucleotide pattern molecule that induces cross-presentation of foreign Ag in myeloid dendritic cells (DC) and MHC Class I-dependent proliferation of cytotoxic T lymphocytes (CTL). DC (BM or spleen CD8α+) have sensors for dsRNA including polyI:C to signal facilitating cross-presentation. Endosomal TLR3 and cytoplasmic RIG-I/MDA5 are reportedly responsible for polyI:C sensing and presumed to deliver signal for cross-presentation via TICAM-1 (TRIF) and IPS-1 (MAVS, Cardif, VISA) adaptors, respectively. In fact, when tumor-associated Ag (TAA) was simultaneously taken up with polyI:C in DC, the DC cross-primed CTL specific to the TAA in a syngenic mouse model. Here we tested which of the TICAM-1 or IPS-1 pathway participate in cross-presentation of tumor-associated soluble Ag and retardation of tumor growth in the setting with a syngeneic tumor implant system, EG7/C57BL6, and exogenously challenged soluble Ag (EG7 lysate) and polyI:C. When EG7 lysate and polyI:C were subcutaneously injected in tumor-bearing mice, EG7 tumor growth retardation was observed in wild-type and to a lesser extent IPS-1−/− mice, but not TICAM-1−/− mice. IRF-3/7 were essential but IPS-1 and type I IFN were minimally involved in the polyI:C-mediated CTL proliferation. Although both TICAM-1 and IPS-1 contributed to CD86/CD40 upregulation in CD8α+ DC, H2Kb-SL8 tetramer and OT-1 proliferation assays indicated that OVA-recognizing CD8 T cells predominantly proliferated in vivo through TICAM-1 and CD8α+ DC is crucial in ex vivo analysis. Ultimately, tumor regresses > 8 d post polyI:C administration. The results infer that soluble tumor Ag induces tumor growth retardation, i.e., therapeutic potential, if the TICAM-1 signal coincidentally occurs in CD8α+ DC around the tumor." @default.
• W2016268206 created "2016-06-24" @default.
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• W2016268206 date "2012-08-01" @default.
• W2016268206 modified "2023-09-23" @default.
• W2016268206 title "Cross-priming for antitumor CTL induced by soluble Ag + polyI:C depends on the TICAM-1 pathway in mouse CD11c⁺/CD8α⁺dendritic cells" @default.
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• W2016268206 doi "https://doi.org/10.4161/onci.19893" @default.
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