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Publication : Oxidized lipids block antigen cross-presentation by dendritic cells in cancer.

First Author  Ramakrishnan R Year  2014
Journal  J Immunol Volume  192
Issue  6 Pages  2920-31
PubMed ID  24554775 Mgi Jnum  J:209897
Mgi Id  MGI:5568885 Doi  10.4049/jimmunol.1302801
Citation  Ramakrishnan R, et al. (2014) Oxidized lipids block antigen cross-presentation by dendritic cells in cancer. J Immunol 192(6):2920-31
abstractText  Cross-presentation is one of the main features of dendritic cells (DCs), which is critically important for the development of spontaneous and therapy-inducible antitumor immune responses. Patients, at early stages of cancer, have normal presence of DCs. However, the difficulties in the development of antitumor responses in patients with low tumor burden raised the question of the mechanisms of DC dysfunction. In this study, we found that, in differentiated DCs, tumor-derived factors blocked the cross-presentation of exogenous Ags without inhibiting the Ag presentation of endogenous protein or peptides. This effect was caused by intracellular accumulation of different types of oxidized neutral lipids: triglycerides, cholesterol esters, and fatty acids. In contrast, the accumulation of nonoxidized lipids did not affect cross-presentation. Oxidized lipids blocked cross-presentation by reducing the expression of peptide-MHC class I complexes on the cell surface. Thus, this study suggests the novel role of oxidized lipids in the regulation of cross-presentation.
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