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Lipid accumulation and dendritic cell dysfunction in cancer.

Authors
Herber-DL; Cao-W; Nefedova-Y; Novitskiy-SV; Nagaraj-S; Tyurin-VA; Corzo-A; Cho-HI; Celis-E; Lennox-B; Knight-SC; Padhya-T; McCaffrey-TV; McCaffrey-JC; Antonia-S; Fishman-M; Ferris-RL; Kagan-VE; Gabrilovich-DI
Source
Nat Med 2010 Aug; 16(8):880-886
NIOSHTIC No.
20037572
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.
Keywords
Cell-function; Immune-reaction; Animals; Humans; Lipids; Tumors; Antigens; Cancer
Contact
Dmitry I Gabrilovich, Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA
CODEN
NAMEFI
Publication Date
20100801
Document Type
Journal Article
Email Address
dmitry.gabrilovich@moffitt.org
Funding Type
Grant
Fiscal Year
2010
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282
Issue of Publication
8
ISSN
1078-8956
Source Name
Nature Medicine
State
FL; PA
Performing Organization
University of Pittsburgh at Pittsburgh
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