PMID- 20622859
OWN - NLM
STAT- MEDLINE
DCOM- 20100831
LR  - 20211020
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 16
IP  - 8
DP  - 2010 Aug
TI  - Lipid accumulation and dendritic cell dysfunction in cancer.
PG  - 880-6
LID - 10.1038/nm.2172 [doi]
AB  - 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.
FAU - Herber, Donna L
AU  - Herber DL
AD  - Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
FAU - Cao, Wei
AU  - Cao W
FAU - Nefedova, Yulia
AU  - Nefedova Y
FAU - Novitskiy, Sergey V
AU  - Novitskiy SV
FAU - Nagaraj, Srinivas
AU  - Nagaraj S
FAU - Tyurin, Vladimir A
AU  - Tyurin VA
FAU - Corzo, Alex
AU  - Corzo A
FAU - Cho, Hyun-Il
AU  - Cho HI
FAU - Celis, Esteban
AU  - Celis E
FAU - Lennox, Brianna
AU  - Lennox B
FAU - Knight, Stella C
AU  - Knight SC
FAU - Padhya, Tapan
AU  - Padhya T
FAU - McCaffrey, Thomas V
AU  - McCaffrey TV
FAU - McCaffrey, Judith C
AU  - McCaffrey JC
FAU - Antonia, Scott
AU  - Antonia S
FAU - Fishman, Mayer
AU  - Fishman M
FAU - Ferris, Robert L
AU  - Ferris RL
FAU - Kagan, Valerian E
AU  - Kagan VE
FAU - Gabrilovich, Dmitry I
AU  - Gabrilovich DI
LA  - eng
GR  - R01 HL070755/HL/NHLBI NIH HHS/United States
GR  - R01 OH008282/OH/NIOSH CDC HHS/United States
GR  - K24 CA128953/CA/NCI NIH HHS/United States
GR  - G0500677/MRC_/Medical Research Council/United Kingdom
GR  - HL094488/HL/NHLBI NIH HHS/United States
GR  - OH008282/OH/NIOSH CDC HHS/United States
GR  - R21 AI070598-02/AI/NIAID NIH HHS/United States
GR  - HL70755/HL/NHLBI NIH HHS/United States
GR  - R21 AI070598/AI/NIAID NIH HHS/United States
GR  - R01 HL094488/HL/NHLBI NIH HHS/United States
GR  - 1R21AI070598/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100711
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)
RN  - 0 (Boron Compounds)
RN  - 0 (Fatty Acids)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Msr1 protein, mouse)
RN  - 0 (Scavenger Receptors, Class A)
SB  - IM
CIN - Nat Med. 2010 Aug;16(8):858-9. PMID: 20689548
MH  - Animals
MH  - Boron Compounds/pharmacokinetics
MH  - Dendritic Cells/immunology/pathology/*physiology
MH  - Fatty Acids/analysis/pharmacokinetics
MH  - Fluorescent Dyes/pharmacokinetics
MH  - Humans
MH  - Lipid Metabolism/*physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neoplasm Transplantation
MH  - Neoplasms/*immunology/*metabolism/pathology/physiopathology
MH  - Scavenger Receptors, Class A/genetics/metabolism
MH  - Spectrometry, Mass, Electrospray Ionization
MH  - Tumor Cells, Cultured
PMC - PMC2917488
MID - NIHMS209643
COIS- Authors declare no competing financial interests.
EDAT- 2010/07/14 06:00
MHDA- 2010/09/02 06:00
PMCR- 2011/02/01
CRDT- 2010/07/13 06:00
PHST- 2009/11/13 00:00 [received]
PHST- 2010/05/27 00:00 [accepted]
PHST- 2010/07/13 06:00 [entrez]
PHST- 2010/07/14 06:00 [pubmed]
PHST- 2010/09/02 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - nm.2172 [pii]
AID - 10.1038/nm.2172 [doi]
PST - ppublish
SO  - Nat Med. 2010 Aug;16(8):880-6. doi: 10.1038/nm.2172. Epub 2010 Jul 11.