Immunosurveillance of lung melanoma metastasis in EBI-3-deficient mice mediated by CD8+ T cells

Kerstin A. Sauer, Joachim H. Maxeiner, Roman Karwot, Petra Scholtes, Hans A. Lehr, Mark Birkenbach, Richard S. Blumberg, Susetta Finotto

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22 Scopus citations

Abstract

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-γproducing 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.

Original languageEnglish (US)
Pages (from-to)6148-6157
Number of pages10
JournalJournal of Immunology
Volume181
Issue number9
DOIs
StatePublished - Nov 1 2008

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    Sauer, K. A., Maxeiner, J. H., Karwot, R., Scholtes, P., Lehr, H. A., Birkenbach, M., Blumberg, R. S., & Finotto, S. (2008). Immunosurveillance of lung melanoma metastasis in EBI-3-deficient mice mediated by CD8+ T cells. Journal of Immunology, 181(9), 6148-6157. https://doi.org/10.4049/jimmunol.181.9.6148