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Cancer Immunology, Immunotherapy

, Volume 55, Issue 6, pp 708–716 | Cite as

Early-outgrowth of endothelial progenitor cells can function as antigen-presenting cells

  • Masahiro AsakageEmail author
  • Nelson H. Tsuno
  • Joji Kitayama
  • Kazushige Kawai
  • Yurai Okaji
  • Kentaro Yazawa
  • Shoichi Kaisaki
  • Takuya Osada
  • Toshiaki Watanabe
  • Koki Takahashi
  • Hirokazu Nagawa
Original Article

Abstract

Endothelial progenitor cells (EPCs) have been recently found to exist circulating in peripheral blood of adults, and home to sites of neovascularization in peripheral tissues. They can also be differentiated from peripheral blood mononuclear cells (PBMNCs). In tumor tissues, EPCs are found in highly vascularized lesions. Few reports exist in the literature concerning the characteristics of EPCs, especially related to their surface antigen expressions, except for endothelial markers. Here, we aimed to investigate the surface expression of differentiation markers, and the functional activities of early-outgrowth of EPCs (EO-EPCs), especially focusing on their antigen-presenting ability. EO-EPCs were generated from PBMNCs, by culture in the presence of angiogenic factors. These EO-EPCs had the morphological and functional features of endothelial cells and, additionally, they shared antigen-presenting ability. They induced the proliferation of allogeneic lymphocytes in a mixed-lymphocyte reaction, and could generate cytotoxic lymphocytes, with the ability to lyze tumor cells in an antigen-specific manner. The antigen-presenting ability of EO-EPCs, however, was weaker than that of monocyte-derived dendritic cells, but stronger than peripheral blood monocytes. Since EO-EPCs play an important role in the development of tumor angiogenesis, targeting EPCs would be an effective anti-angiogenic strategy. Alternatively, due to their antigen-presenting ability, EO-EPCs can be used as the effectors of anti-tumor immunotherapy. Since they share endothelial antigens, the activation of a cellular immunity against angiogenic vessels can be expected. In conclusion, EO-EPCs should be an interesting alternative for the development of new therapeutic strategies to combat cancer, either as the effectors or as the targets of cancer immunotherapy.

Keywords

Early-outgrowth of endothelial progenitor cells Endothelial progenitor cells Angiogenesis Antigen presenting cells 

Abbreviations

EPCs

Endothelial progenitor cells

EO-EPCs

Early-outgrowth of endothelial progenitor cells

ECs

Endothelial cells

PBMNCs

Peripheral blood mononuclear cells

aFGF

Acidic fibroblast growth factor

DiLDL

1, 1′-Dioctadecyl-3, 3, 3′, 3′-tetramethylindocarbocyanine-labeled acetylated low-density lipoprotein

APC

Antigen-presenting cells

CTL

Cytotoxic T lymphocytes

Mo-DCs

Monocyte-derived dendritic cells

HUVECs

Human umbilical vein endothelial cells

FCS

Fetal calf serum

MLR

Mixed lymphocytes reaction

FITC

Fluorescein isothiocyanate

Notes

Acknowledgements

This study was supported partly by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, partly by a grant from the Ministry of Health, Labour and Welfare of Japan, and partly by a grant from the Sankyo Foundation of Life Science.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Masahiro Asakage
    • 1
    Email author
  • Nelson H. Tsuno
    • 1
    • 2
  • Joji Kitayama
    • 1
  • Kazushige Kawai
    • 1
  • Yurai Okaji
    • 1
  • Kentaro Yazawa
    • 1
  • Shoichi Kaisaki
    • 1
  • Takuya Osada
    • 1
  • Toshiaki Watanabe
    • 1
  • Koki Takahashi
    • 2
  • Hirokazu Nagawa
    • 1
  1. 1.Department of Surgical OncologyThe University of TokyoTokyoJapan
  2. 2.Department of Transfusion Medicine, Faculty of MedicineThe University of TokyoTokyoJapan

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