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RESEARCH PRODUCT
Immunosurveillance of lung melanoma metastasis in EBI-3-deficient mice mediated by CD8+ T cells.
Richard S. BlumbergHans A. LehrPetra ScholtesJoachim MaxeinerMark BirkenbachRoman KarwotKerstin A SauerSusetta Finottosubject
Cytotoxicity ImmunologicAdoptive cell transferLung NeoplasmsT cellImmunologyMelanoma ExperimentalBiologyCD8-Positive T-LymphocytesArticleMetastasisMinor Histocompatibility AntigensGene Knockout TechniquesMiceCell Line TumormedicineImmunology and AllergyCytotoxic T cellAnimalsLung MelanomaReceptors CytokineImmunologic SurveillanceCell Line TransformedMice KnockoutMelanomamedicine.diseaseImmunosurveillanceMice Inbred C57BLmedicine.anatomical_structureCell Transformation NeoplasticImmunologyInjections IntravenousAnimals; CD8-Positive T-Lymphocytes; Cell Line Transformed; Cell Line Tumor; Cell Transformation Neoplastic; Cytotoxicity Immunologic; Gene Knockout Techniques; Immunologic Surveillance; Injections Intravenous; Lung Neoplasms; Melanoma Experimental; Mice; Mice Inbred C57BL; Mice Knockout; Neoplasm Transplantation; Receptors Cytokine; T-Box Domain ProteinsCancer researchT-Box Domain ProteinsCD8Neoplasm Transplantationdescription
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-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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-11-01 |