Influenza a infection enhances cross-priming of CD8+ T cells to cell-associated antigens in a TLR7-and type I IFN-dependent fashion

The initiation of antitumor immunity relies on dendritic cells (DCs) to cross-present cell-associated tumor Ag to CD8 T cells (T ) due to a lack of costimulatory molecules on tumor cells. Innate danger signals have been demonstrated to enhance crosspriming of T to soluble as well as virally encoded Ags; however, their effect on enhancing T cross-priming to cell genomeencoded Ags remains unknown. Furthermore, influenza A virus (IAV) has not been shown to enhance antitumor immunity. Using influenza-infected allogeneic cell lines, we show in this study that T responses to cell-associated Ags can be dramatically enhanced due to enhanced T 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-induced IL-1 and IFN-γ 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 APCs able to prime TCR-transgenic T . Importantly, plasmacytoid DCs and CD8 DCs were both able to enhance such priming when provided in coculture. 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