title: Lipid accumulation and dendritic cell dysfunction in cancer.
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.
authors.affiliation: Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Herber
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Yulia
authors.initials: Y
authors.lastname: Nefedova
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Novitskiy
authors.forename: Srinivas
authors.initials: S
authors.lastname: Nagaraj
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Tyurin
authors.forename: Alex
authors.initials: A
authors.lastname: Corzo
authors.forename: Hyun-Il
authors.initials: HI
authors.lastname: Cho
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
authors.forename: Brianna
authors.initials: B
authors.lastname: Lennox
authors.forename: Stella C
authors.initials: SC
authors.lastname: Knight
authors.forename: Tapan
authors.initials: T
authors.lastname: Padhya
authors.forename: Thomas V
authors.initials: TV
authors.lastname: McCaffrey
authors.forename: Judith C
authors.initials: JC
authors.lastname: McCaffrey
authors.forename: Scott
authors.initials: S
authors.lastname: Antonia
authors.forename: Mayer
authors.initials: M
authors.lastname: Fishman
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Gabrilovich
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000493:pharmacokinetics; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D005227:Fatty Acids / Q000032:analysis / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D014407:Tumor Cells, Cultured
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005227:Fatty Acids; D005456:Fluorescent Dyes; C495140:Msr1 protein, mouse; D051117:Scavenger Receptors, Class A