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

Wei Cao, Rupal Ramakrishnan, Vladimir A. Tuyrin, Filippo Veglia, Thomas Condamine, Andrew Amoscato, Dariush Mohammadyani, Joseph J. Johnson, Lan Min Zhang, Judith Klein-Seetharaman, Esteban Celis, Valerian E. Kagan, Dmitry I. Gabrilovich

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

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 crosspresentation 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. The Journal of Immunology, 2014, 192: 2920-2931.

Original languageEnglish (US)
Pages (from-to)2920-2931
Number of pages12
JournalJournal of Immunology
Volume192
Issue number6
DOIs
StatePublished - Mar 15 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Cao, W., Ramakrishnan, R., Tuyrin, V. A., Veglia, F., Condamine, T., Amoscato, A., Mohammadyani, D., Johnson, J. J., Zhang, L. M., Klein-Seetharaman, J., Celis, E., Kagan, V. E., & Gabrilovich, D. I. (2014). Oxidized lipids block antigen cross-presentation by dendritic cells in cancer. Journal of Immunology, 192(6), 2920-2931. https://doi.org/10.4049/jimmunol.1302801