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Oxidized lipids block antigen cross-presentation by dendritic cells in cancer
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Cao, W., Ramakrishnan, R., Tuyrin, V. A., Veglia, F., Condamine, T., Amoscato, A., Mohammadyani, D., Johnson, J. J., Min Zhang, L., Klein-Seetharaman, Judith, Celis, E., Kagan, V. E. and Gabrilovich, D. I. (2014) Oxidized lipids block antigen cross-presentation by dendritic cells in cancer. The Journal of Immunology, Volume 192 (Number 6). pp. 2920-2931. doi:10.4049/jimmunol.1302801 ISSN 0022-1767.
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Official URL: http://dx.doi.org/10.4049/jimmunol.1302801
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 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.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | The Journal of Immunology | ||||||
| Publisher: | American Association of Immunologists | ||||||
| ISSN: | 0022-1767 | ||||||
| Official Date: | 15 March 2014 | ||||||
| Dates: |
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| Volume: | Volume 192 | ||||||
| Number: | Number 6 | ||||||
| Page Range: | pp. 2920-2931 | ||||||
| DOI: | 10.4049/jimmunol.1302801 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||
| Description: | Errata - May 15, 2014 http://www.jimmunol.org/content/192/10/4935 |
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