A study of dendritic and endothelial cell interactions in colon cancer in a cell line and small mammal model.
OBJECTIVE
Historically, cancer therapy directly targeting tumor cells have yielded suboptimal clinical results, and therefore anti-angiogenic therapy that targets tumor cells indirectly through impairing tumor vasculature is now considered to be one of the novel approaches potentially effective against various types of cancer. In this study, we evaluated whether lysates of endothelium could be effectively pulsed in dendritic cells (DCs), to enhance their anti-tumor effects.


METHODS
For this purpose, we prepared DCs of BALB/c mouse, incubated them with lysates of autologous or xenogeneic endothelium, and tested their anti-tumor effects in two syngeneic models of colon cancer.


RESULTS
DCs pulsed with the respective endothelium lysates significantly inhibited the growth of subcutaneous tumors as well as pulmonary metastases in mice, and their anti-tumor effect was superior to that of unpulsed DCs. Immunohistopathological analysis showed significant decrease in the mean vascular density of tumors, correlating well with the extent of tumor inhibition. In vitro analysis of splenocytes isolated from immunized mice revealed an induction of cytotoxic T lymphocytes and activation of natural killer cells, with a lytic activity against activated endothelium but not tumor cells. In addition, antibodies reacting with activated endothelium, but not tumor cells, were detected in murine sera by ELISA, and their function was confirmed by complement-dependent cytotoxicity assay.


CONCLUSIONS
Our present results suggest that lysates of endothelium can be effectively pulsed in DCs and enhance their anti-tumor effects through induction of anti-angiogenesis, and therefore should have important clinical implications for adjuvant cancer therapy.
Yoneyama
S
S
Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. yoneyamas-tky@umin.ac.jp
Okaji
Y
Y
Tsuno
N H
NH
Kawai
K
K
Yamashita
H
H
Tsuchiya
T
T
Yamada
J
J
Sunami
E
E
Osada
T
T
Kitayama
J
J
Takahashi
K
K
Nagawa
H
H
D000818:Animals; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines