| First Author | Boudreau JE | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 7 | Pages | 2497-506 |
| PubMed ID | 21307131 | Mgi Jnum | J:170909 |
| Mgi Id | MGI:4947885 | Doi | 10.1158/0008-5472.CAN-10-3025 |
| Citation | Boudreau JE, et al. (2011) IL-15 and Type I Interferon Are Required for Activation of Tumoricidal NK Cells by Virus-Infected Dendritic Cells. Cancer Res 71(7):2497-506 |
| abstractText | There is increasing evidence that natural killer (NK) cells play an important role in antitumor immunity following dendritic cell (DC) vaccination. Little is known, however, about the optimal stimulation of DCs that favors NK activation in tumor-bearing hosts. In this study, we demonstrate that treatment with toll-like receptor (TLR) ligands and infection with a mutant vesicular stomatitis virus (VSV-DeltaM51) both induced DC maturation. Further, inoculation of these DCs led to robust NK-mediated protection against tumor challenge. Strikingly, only VSV-DeltaM51-infected DCs were capable of suppressing the growth of established tumors, suggesting that additional signals provided by viral infection may be required to activate tumoricidal NK cells in tumor-bearing hosts. VSV-DeltaM51 infection of DCs induced greater type I interferon (IFN I) production than TLR ligand treatment, and disruption of the IFN I pathway in DCs eliminated their ability to induce NK activation and tumor protection. However, further studies indicated that IFN I alone was not sufficient to activate NK cells, especially in the presence of a tumor, and DC-derived IL-15 was additionally required for tumoricidal NK activation. These results suggest that induction of IFN I by VSV-DeltaM51 allows DCs to overcome tumor-associated immunosuppression and facilitate IL-15-mediated priming of tumoricidal NK cells. Thus, the mode of DC maturation should be carefully considered when designing DC-based cancer immunotherapies. Cancer Res; 71(7); 2497-506. (c)2011 AACR. |
