Fiche publication
Date publication
novembre 2015
Journal
The Journal of investigative dermatology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FLACHER Vincent
Tous les auteurs :
Mairhofer DG, Ortner D, Tripp CH, Schaffenrath S, Fleming V, Heger L, Komenda K, Reider D, Dudziak D, Chen S, Becker JC, Flacher V, Stoitzner P
Lien Pubmed
Résumé
Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In the present study, we characterized the immune status and functional properties of immune cells in tumor-bearing mice. Melanoma development was accompanied by a reduction in the percentages of CD4(+) T cells including regulatory T cells (Tregs) in CD45(+) leukocytes present in tumor tissue and draining lymph nodes (LNs). In contrast, the percentages of CD8(+) T cells were unchanged, and these cells showed an activated phenotype in tumor mice. Endogenous melanoma-associated antigen glycoprotein 100 (gp100)-specific CD8(+) T cells were not deleted during tumor development, as revealed by pentamer staining in the skin and draining LNs. They, however, were unresponsive to ex vivo gp100-peptide stimulation in late-stage tumor mice. Interestingly, immunosuppressive myeloid-derived suppressor cells (MDSCs) were recruited to tumor tissue with a preferential accumulation of granulocytic MDSC (grMDSCs) over monocytic MDSC (moMDSCs). Both subsets produced Arginase-1, inducible nitric oxide synthase (iNOS), and transforming growth factor-β and suppressed T-cell proliferation in vitro. In this work, we describe the immune status of a spontaneous melanoma mouse model that provides an interesting tool to develop future immunotherapeutical strategies.
Mots clés
Analysis of Variance, Animals, CD8-Positive T-Lymphocytes, immunology, Cell Proliferation, Disease Models, Animal, Humans, Lymphocyte Activation, Melanoma, Experimental, immunology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Random Allocation, Suppressor Factors, Immunologic, immunology, T-Lymphocytes, Regulatory, immunology, Tumor Cells, Cultured, gp100 Melanoma Antigen, immunology
Référence
J Invest Dermatol. 2015 Nov;135(11):2785-2793
