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- W1008155287 abstract "Abstract MUC1 is a tumor-associated antigen. MUC1-specific TCR transgenic CD4+ T cells transferred into MUC1 Tg mice show less proliferation in response to vaccination with DC loaded with MUC1 peptide (DC/MUC1p) compared to WT. To query the underlying regulatory mechanisms, we vaccinated WT and Tg mice with DC/MUC1p and conducted transciptome analysis of splenic RNA. Proteases previously characterized as pancreas-restricted (Trypsin, Elastase and Carboxypeptidase B1) were significantly down-regulated in splenic DC from Tg mice relative to WT. Vaccination with soluble MUC1p gave the same result. Protease mRNA down-regulation in DC correlated with the reduction at the protein level. In related work we have shown that these enzymes are regulated by DC/T effector versus T reg interactions. Inhibition of Trypsin or CPB1 decreases the ability of DC to elicit MUC1-specific CD4 T cell response in vitro, supporting a correlation between deficient protease expression in DC and reduced T cell response in vivo. DC from MUC1p-vaccinated Tg mice express lower levels of MHC II and costimulatory molecules concurrent with decreased protease levels. These proteases are found in MHC II+ and lysosomal compartments, sites of antigen processing. We suggest that one mechanism of peripheral tolerance that regulates anti-MUC1 immunity is inhibition of antigen processing. We propose that pharmacologic modulation of these enzymes could be one approach to improving the potency of TAA-based cancer vaccines." @default.
- W1008155287 created "2016-06-24" @default.
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- W1008155287 date "2011-04-01" @default.
- W1008155287 modified "2023-09-25" @default.
- W1008155287 title "Regulation of expression of “pancreatic” proteases in dendritic cells: a novel mechanism of peripheral tolerance (100.34)" @default.
- W1008155287 doi "https://doi.org/10.4049/jimmunol.186.supp.100.34" @default.
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