Influenza A infection enhances cross-priming of CD8+ T cells to cell-associated antigens in a TLR7- and type I interferon-dependent fashion (92.6)

Abstract

The initiation of anti-tumor immunity relies on DCs to cross-present cell-associated tumor antigen to CD8+ T cells due to a lack of co-stimulatory molecules on tumor cells. Innate danger signals have been demonstrated to enhance cross-priming of TCD8+ to soluble as well as virally encoded Ags, however their effect on enhancing TCD8+ cross-priming to cell-genome encoded Ags remains unknown. Furthermore, Influenza A virus has not been shown to enhance anti-tumor immunity. Using influenza-infected allogeneic cell lines, we show here that TCD8+ responses to cell-associated Ags can be dramatically enhanced due to enhanced TCD8+ expansion. This enhanced cross-priming in part involves TLR7-, but not TLR3-, mediated sensing of IAV and is entirely dependent on MyD88 and IFN signaling pathways. We also showed that the inflammasome and IFN-r did not play a role in enhancing cross-priming in our system. We further demonstrated in our ex vivo system that CD8+ DCs are the only antigen-presenting cells able to prime TCR transgenic TCD8+. Importantly, pDCs and CD8- DCs were all able to enhance such priming when provided in co-culture. These observations suggest that IAV-infection of tumor cells may facilitate improved cross-presentation of tumor Ags and may be used to augment clinical vaccine efficacy.