Lipid accumulation and dendritic cell dysfunction in cancer

Donna L. Herber, Wei Cao, Yulia Nefedova, Sergey V. Novitskiy, Srinivas Nagaraj, Vladimir A. Tyurin, Alex Corzo, Hyun Ii Cho, Esteban Celis, Brianna Lennox, Stella C. Knight, Tapan Padhya, Thomas V. McCaffrey, Judith C. McCaffrey, Scott Antonia, Mayer Fishman, Robert L. Ferris, Valerian E. Kagan, Dmitry I. Gabrilovich

Research output: Contribution to journalArticle

265 Scopus citations

Abstract

Dendritic cells (DCs), a type of professional antigen-presenting cells, are responsible for initiation and maintenance of immune responses. Here we report that a substantial proportion of DCs in tumor-bearing mice and people with cancer have high amounts of triglycerides as compared with DCs from tumor-free mice and healthy individuals. In our studies, lipid accumulation in DCs was caused by increased uptake of extracellular lipids due to upregulation of scavenger receptor A. DCs with high lipid content were not able to effectively stimulate allogeneic T cells or present tumor-associated antigens. DCs with high and normal lipid levels did not differ in expression of major histocompatibility complex and co-stimulatory molecules. However, lipid-laden DCs had a reduced capacity to process antigens. Pharmacological normalization of lipid abundance in DCs with an inhibitor of acetyl-CoA carboxylase restored the functional activity of DCs and substantially enhanced the effects of cancer vaccines. These findings suggest that immune responses in cancer can be improved by manipulating the lipid levels in DCs.

Original languageEnglish (US)
Pages (from-to)880-886
Number of pages7
JournalNature Medicine
Volume16
Issue number8
DOIs
StatePublished - Aug 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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