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Molecular Medicine

, Volume 17, Issue 9–10, pp 910–916 | Cite as

Effect of Oxygen Levels on the Physiology of Dendritic Cells: Implications for Adoptive Cell Therapy

  • Diahnn Futalan
  • Chien-Tze Huang
  • Ingo G. H. Schmidt-Wolf
  • Marie Larsson
  • Davorka Messmer
Research Article

Abstract

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 CO2 incubators under atmospheric oxygen conditions (21% O2), 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)-α 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.

Notes

Acknowledgments

This work was supported by the U.S. Army Medical Research and Materiel Command under agreement number W81XWH-07-1-0412 to D Messmer, the Swedish Research Council AI52731 and the Swedish International Development Cooperation Agency (SIDA and VINNMER [Vinnova]) to M Larsson. The authors thank Jessie F Fecteau and Dan Seible for the critical reading of the manuscript.

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Copyright information

© The Feinstein Institute for Medical Research 2011
www.feinsteininstitute.org

Authors and Affiliations

  • Diahnn Futalan
    • 1
  • Chien-Tze Huang
    • 1
  • Ingo G. H. Schmidt-Wolf
    • 2
  • Marie Larsson
    • 3
  • Davorka Messmer
    • 1
  1. 1.Moores Cancer CenterUniversity of California San DiegoLa JollaUSA
  2. 2.Department of Internal MedicineRheinische Friedrich-Wilhelms UniversitaetBonnGermany
  3. 3.Division of Molecular Virology, Department of Clinical and Experimental MedicineLinköping UniversityLinköpingSweden

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