Lipid bodies containing oxidatively truncated lipids block antigen cross-presentation by dendritic cells in cancer.

Published online

Journal Article

Cross-presentation is a critical function of dendritic cells (DCs) required for induction of antitumor immune responses and success of cancer immunotherapy. It is established that tumor-associated DCs are defective in their ability to cross-present antigens. However, the mechanisms driving these defects are still unknown. We find that impaired cross-presentation in DCs is largely associated with defect in trafficking of peptide-MHC class I (pMHC) complexes to the cell surface. DCs in tumor-bearing hosts accumulate lipid bodies (LB) containing electrophilic oxidatively truncated (ox-tr) lipids. These ox-tr-LB, but not LB present in control DCs, covalently bind to chaperone heat shock protein 70. This interaction prevents the translocation of pMHC to cell surface by causing the accumulation of pMHC inside late endosomes/lysosomes. As a result, tumor-associated DCs are no longer able to stimulate adequate CD8 T cells responses. In conclusion, this study demonstrates a mechanism regulating cross-presentation in cancer and suggests potential therapeutic avenues.

Full Text

Duke Authors

Cited Authors

  • Veglia, F; Tyurin, VA; Mohammadyani, D; Blasi, M; Duperret, EK; Donthireddy, L; Hashimoto, A; Kapralov, A; Amoscato, A; Angelini, R; Patel, S; Alicea-Torres, K; Weiner, D; Murphy, ME; Klein-Seetharaman, J; Celis, E; Kagan, VE; Gabrilovich, DI

Published Date

  • December 14, 2017

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 2122 -

PubMed ID

  • 29242535

Pubmed Central ID

  • 29242535

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-017-02186-9

Language

  • eng

Conference Location

  • England