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Inclusive estimation of complex antigen presentation functions of monocyte-derived dendritic cells differentiated under normoxia and hypoxia conditions

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Abstract

Dendritic cells (DCs) generated from monocytes under 20% O2 are now used as therapeutic tools for cancer patients. However, the O2 concentration is between 3 and 0.5% in most tissues. We evaluated these complicated functions of DCs under oxygen tensions mimicking in vivo situations. Immature DCs (imDCs) were generated from monocytes using IL-4 and GM-CSF under normoxia (20% O2; N-imDCs) or hypoxia (1% O2; H-imDCs). Mature DCs (mDCs) were induced with LPS. DCs were further exposed to normoxia (N/N-DCs) or hypoxia (N/H-DCs and H/H-DCs) conditions. Using a 2-D culture system, H-DCs were smaller in size than N-DCs, and H/H-DCs exhibited higher allo-T cell stimulation ability than N/N-DCs and N/H-DCs. On the other hand, motility and phagocytic ability of H/H-DCs were significantly lower than those of N/H-DCs and N/N-DCs. In a 3-D culture system, however, maturation of H/H-imDCs and N/H-imDCs was suppressed compared with N/N-imDCs as a result of their decreased motility and phagocytosis. Interestingly, silencing of HIF-1α by RNA interference decreased CD83 expression without affecting any antigen presentation abilities except for the ability to stimulate the allo-T cell population. Our data could help our understanding of DCs, especially therapeutic DCs, in vivo.

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Abbreviations

MFI:

Mean fluorescence intensity

VEGF:

Vascular endothelial cell growth factor

HIF-1α:

Hypoxia inducible factor-1α

Treg:

Regulatory T cell

CA9:

Carbonic anhydrase IX

3-D:

Three-dimensional

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Acknowledgments

We thank Kaori Nomiyama for her skillful technical assistance.

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Authors and Affiliations

  1. Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Toshitatsu Ogino, Hideya Onishi, Hiroyuki Suzuki & Mitsuo Katano

  2. Fukuoka Cancer General Clinic, Fukuoka, Japan

    Takashi Morisaki

  3. Department of Surgery and Oncology, Kyushu University, Fukuoka, Japan

    Masao Tanaka

Authors
  1. Toshitatsu Ogino
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  2. Hideya Onishi
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  3. Hiroyuki Suzuki
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  4. Takashi Morisaki
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  5. Masao Tanaka
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  6. Mitsuo Katano
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Corresponding author

Correspondence to Mitsuo Katano.

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Ogino, T., Onishi, H., Suzuki, H. et al. Inclusive estimation of complex antigen presentation functions of monocyte-derived dendritic cells differentiated under normoxia and hypoxia conditions. Cancer Immunol Immunother 61, 409–424 (2012). https://doi.org/10.1007/s00262-011-1112-5

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  • DOI: https://doi.org/10.1007/s00262-011-1112-5

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