Early-outgrowth of endothelial progenitor cells can function as antigen-presenting cells.
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.
Asakage
Masahiro
M
Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan. asakage-dis@h.u-tokyo.ac.jp
Tsuno
Nelson H
NH
Kitayama
Joji
J
Kawai
Kazushige
K
Okaji
Yurai
Y
Yazawa
Kentaro
K
Kaisaki
Shoichi
S
Osada
Takuya
T
Watanabe
Toshiaki
T
Takahashi
Koki
K
Nagawa
Hirokazu
H
D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000943:Antigens, Differentiation; D015415:Biomarkers / Q000032:analysis; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D009389:Neovascularization, Pathologic / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000943:Antigens, Differentiation; D015415:Biomarkers