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Updated: Feb 16, 2026

An Efficient and High Yield Method for Isolation of Mouse Dendritic Cell Subsets
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Published on: April 18, 2016

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

Filippo Veglia1, Vladimir A Tyurin2, Dariush Mohammadyani2,3

  • 1Translational Tumor Immunology Program, The Wistar Institute, Philadelphia, PA, 19104, USA.

Nature Communications
|December 16, 2017
PubMed

Insights

Tumor-associated dendritic cells (DCs) show impaired antigen cross-presentation due to lipid bodies binding to heat shock protein 70. This defect prevents CD8 T cell activation, hindering anti-tumor immunity.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Trafficking

Background:

  • Dendritic cells (DCs) are crucial for initiating anti-tumor immune responses via antigen cross-presentation.
  • Tumor-associated DCs exhibit defective cross-presentation, but the underlying mechanisms remain unclear.
  • This defect is critical for the efficacy of cancer immunotherapy.

Purpose of the Study:

  • To elucidate the molecular mechanisms behind impaired cross-presentation in tumor-associated dendritic cells.
  • To identify the role of cellular components and trafficking pathways in this defect.

Main Methods:

  • Analysis of dendritic cells from tumor-bearing hosts versus control subjects.
  • Investigation of lipid body composition and associated proteins.
  • Tracking of peptide-MHC class I (pMHC) complex trafficking using microscopy and biochemical assays.

Main Results:

  • Tumor-associated DCs accumulate lipid bodies (LBs) containing specific oxidized lipids (ox-tr lipids).
  • These ox-tr-LBs bind to heat shock protein 70 (HSP70) in a manner distinct from control DCs.
  • HSP70 binding to ox-tr-LBs sequesters peptide-MHC class I (pMHC) complexes within late endosomes/lysosomes, preventing cell surface presentation.
  • This intracellular accumulation of pMHC impairs the ability of DCs to stimulate CD8 T cell responses.

Conclusions:

  • A novel mechanism involving ox-tr-LB and HSP70 interaction impairs DC cross-presentation in cancer.
  • This defect in antigen presentation by DCs contributes to suppressed anti-tumor immunity.
  • Targeting this pathway may offer new therapeutic strategies for enhancing cancer immunotherapy.

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