PMID- 21647537
OWN - NLM
STAT- MEDLINE
DCOM- 20120325
LR  - 20231213
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 17
IP  - 9-10
DP  - 2011 Sep-Oct
TI  - Effect of oxygen levels on the physiology of dendritic cells: implications for 
      adoptive cell therapy.
PG  - 910-6
LID - 10.2119/molmed.2011.00031 [doi]
AB  - Dendritic cell (DC)-based adoptive tumor immunotherapy approaches have shown 
      promising results, but the incidence of tumor regression is low and there is an 
      evident call for identifying culture conditions that produce DCs with a more 
      potent Th1 potential. Routinely, DCs are differentiated in CO(2) incubators under 
      atmospheric oxygen conditions (21% O(2)), which differ from physiological oxygen 
      levels of only 3-5% in tissue, where most DCs reside. We investigated whether 
      differentiation and maturation of DCs under physiological oxygen levels could 
      produce more potent T-cell stimulatory DCs for use in adoptive immunotherapy. We 
      found that immature DCs differentiated under physiological oxygen levels showed a 
      small but significant reduction in their endocytic capacity. The different oxygen 
      levels did not influence their stimuli-induced upregulation of cluster of 
      differentiation 54 (CD54), CD40, CD83, CD86, C-C chemokine receptor type 7 
      (CCR7), C-X-C chemokine receptor type 4 (CXCR4) and human leukocyte antigen 
      (HLA)-DR or the secretion of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha 
      and IL-10 in response to lipopolysaccharide (LPS) or a cytokine cocktail. 
      However, DCs differentiated under physiological oxygen level secreted higher 
      levels of IL-12(p70) after exposure to LPS or CD40 ligand. Immature DCs 
      differentiated at physiological oxygen levels caused increased T-cell 
      proliferation, but no differences were observed for mature DCs with regard to 
      T-cell activation. In conclusion, we show that although DCs generated under 
      atmospheric or physiological oxygen conditions are mostly similar in function and 
      phenotype, DCs differentiated under physiological oxygen secrete larger amounts 
      of IL-12(p70). This result could have implications for the use of ex 
      vivo-generated DCs for clinical studies, since DCs differentiated at 
      physiological oxygen could induce increased Th1 responses in vivo.
FAU - Futalan, Diahnn
AU  - Futalan D
AD  - Moores Cancer Center, University of California San Diego, La Jolla, California, 
      USA.
FAU - Huang, Chien-Tze
AU  - Huang CT
FAU - Schmidt-Wolf, Ingo G H
AU  - Schmidt-Wolf IG
FAU - Larsson, Marie
AU  - Larsson M
FAU - Messmer, Davorka
AU  - Messmer D
LA  - eng
GR  - R01 AI052731/AI/NIAID NIH HHS/United States
GR  - R37 AI052731/AI/NIAID NIH HHS/United States
GR  - AI52731/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110601
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (Antigens, CD)
RN  - 0 (B7-1 Antigen)
RN  - 0 (CD40 Antigens)
RN  - 0 (Immunoglobulins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Antigens, CD/immunology/metabolism
MH  - B7-1 Antigen/immunology/metabolism
MH  - CD40 Antigens/immunology/metabolism
MH  - Cell Differentiation/*drug effects/immunology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/*drug effects/immunology/physiology
MH  - Endocytosis/immunology
MH  - Flow Cytometry
MH  - HeLa Cells
MH  - Humans
MH  - Immunoglobulins/immunology/metabolism
MH  - Immunohistochemistry
MH  - Immunotherapy, Adoptive/methods
MH  - Intercellular Adhesion Molecule-1/immunology/metabolism
MH  - Interleukin-10/immunology/metabolism
MH  - Interleukin-12/immunology/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Lymphocyte Activation/immunology/physiology
MH  - Membrane Glycoproteins/immunology/metabolism
MH  - Neoplasms/immunology/therapy
MH  - Oxygen/metabolism/*pharmacology
MH  - T-Lymphocytes/immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/immunology/metabolism
MH  - CD83 Antigen
PMC - PMC3188869
EDAT- 2011/06/08 06:00
MHDA- 2012/03/27 06:00
PMCR- 2011/06/01
CRDT- 2011/06/08 06:00
PHST- 2011/01/19 00:00 [received]
PHST- 2011/05/19 00:00 [accepted]
PHST- 2011/06/08 06:00 [entrez]
PHST- 2011/06/08 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - molmed.2011.00031 [pii]
AID - 11_31_futalan [pii]
AID - 10.2119/molmed.2011.00031 [doi]
PST - ppublish
SO  - Mol Med. 2011 Sep-Oct;17(9-10):910-6. doi: 10.2119/molmed.2011.00031. Epub 2011 
      Jun 1.