TY - JOUR
T1 - Oxidized lipids block antigen cross-presentation by dendritic cells in cancer
AU - Cao, Wei
AU - Ramakrishnan, Rupal
AU - Tuyrin, Vladimir A.
AU - Veglia, Filippo
AU - Condamine, Thomas
AU - Amoscato, Andrew
AU - Mohammadyani, Dariush
AU - Johnson, Joseph J.
AU - Zhang, Lan Min
AU - Klein-Seetharaman, Judith
AU - Celis, Esteban
AU - Kagan, Valerian E.
AU - Gabrilovich, Dmitry I.
PY - 2014/3/15
Y1 - 2014/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84897506146&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897506146&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1302801
DO - 10.4049/jimmunol.1302801
M3 - Article
C2 - 24554775
AN - SCOPUS:84897506146
SN - 0022-1767
VL - 192
SP - 2920
EP - 2931
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -