Abstract
One chief barrier to cancer immunotherapy is tumor-specific T cell tolerance. Here we compared the ability of hemagglutinin (HA)-encoding recombinant viruses versus 'HA-loaded' dendritic cells to reverse HA-specific CD8 tolerance and to protect mice from tumor challenge. Both vaccines were comparable in activating naive HA-specific CD8+ T cells. However, in circumstances of established tolerance, viral vaccines could break CD8 tolerance in the presence of CD4+CD25+ regulatory T cells, whereas dendritic cell-based vaccines achieved this only after removal of regulatory T cells or the coadministration of a Toll-like receptor (TLR) ligand or irrelevant virus. These results demonstrate that virus provides TLR signals required for bypassing regulatory T cell-mediated tolerance and emphasize the importance of persistent TLR signals for immunotherapy in the setting of established tolerance.
Original language | English (US) |
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Pages (from-to) | 508-515 |
Number of pages | 8 |
Journal | Nature Immunology |
Volume | 5 |
Issue number | 5 |
DOIs | |
State | Published - May 2004 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology