Immunosurveillance of Lung Melanoma Metastasis in EBI-3-Deficient Mice Mediated by CD8+ T Cells1

• Published in: The Journal of immunology (1950) 2008-11, Vol.181 (9), p.6148-6157
• Main Authors: Sauer, Kerstin A., Maxeiner, Joachim H., Karwot, Roman, Scholtes, Petra, Lehr, Hans A., Birkenbach, Mark, Blumberg, Richard S., Finotto, Susetta
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606

EBV-induced gene 3 (EBI-3) codes for a soluble type I receptor homologous to the p40 subunit of IL-12 that is expressed by APCs following activation. In this study, we assessed the role of EBI-3 in a model of lung melanoma metastasis. Intravenous injection of the B16-F10 cell line resulted in a significant reduction of lung tumor metastasis in EBI-3 −/− recipient mice compared with wild-type mice. The immunological finding accompanying this effect was the expansion of a newly described cell subset called IFN- γ producing killer dendritic cells associated with CD8 + T cell responses in the lung of EBI-3 −/− mice including IFN- γ release and TNF- α -induced programmed tumor cell death. Depletion of CD8 + T cells as well as targeting T-bet abrogated the protective effects of EBI-3 deficiency on lung melanoma metastases. Finally, adoptive transfer of EBI-3 −/− CD8 + T cells into tumor bearing wild-type mice inhibited lung metastasis in recipient mice. Taken together, these data demonstrate that targeting EBI-3 leads to a T-bet-mediated antitumor CD8 + T cell responses in the lung.