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A Synthetic Peptide Homologous to Functional Domain of Human IL-10 Down-Regulates Expression of MHC Class I and Transporter Associated with Antigen Processing 1/2 in Human Melanoma Cells¹

Mónica Kurte^*, Mercedes López^*, Adam Aguirre^*, Alejandro Escobar^*, Juan Carlos Aguillón^*, Jehad Charo, Christian G. Larsen, Rolf Kiessling and Flavio Salazar-Onfray^2,*

^* Disciplinary Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Department of Oncology and Pathology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden; Department of Dermatology, Marselisborg Hospital, University of Aarhus, Aarhus C, Denmark; and Max-Delbruck-Center for Molecular Medicine, Berlin, Germany

Tumor cells treated with IL-10 were shown to have decreased, but peptide-inducible expression of MHC class I, decreased sensitivity to MHC class I-restricted CTL, and increased NK sensitivity. These findings could be explained, at least partially, by a down-regulation of TAP1/TAP2 expression. In this study, IT9302, a nanomeric peptide (AYMTMKIRN), homologous to the C-terminal of the human IL-10 sequence, was demonstrated to mimic these previously described IL-10 effects on MHC class I-related molecules and functions. We observed a dose-dependent down-regulation of MHC class I at the cell surface of melanoma cells after 24-h treatment with IT9302. The IL-10 homologue peptide also caused a dose-dependent inhibition of the IFN--mediated surface induction of MHC class I in a melanoma cell line. We demonstrated, using Western blot and flow cytometry, that IT9302 inhibits the expression of TAP1 and TAP2 proteins, but not MHC class I H chain or low molecular protein molecules. Finally, peptide-treated melanoma cells were shown to be more sensitive to lysis by NK cells in a dose-dependent way. Taken together, these results demonstrate that a small synthetic peptide derived from IL-10 can mimic the Ag presentation-related effects mediated by this cytokine in human melanomas and increase tumor sensitivity to NK cells, which can be relevant in the designing of future strategies for cancer immune therapy.

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