Dendritic cells fused with human cancer cells: morphology, antigen expression, and T cell stimulation.
Fusion of human dendritic cells (DC) with tumor cells is an effective approach for delivering tumor antigens to DC, and DC/tumor fusion cells are potent stimulators of autologous T cells. However, the integration and morphology of DC/tumor fusion cells has not been examined. In the present study, we fused patient-derived DC to autologous breast or ovarian carcinoma cells. The fusion cells possessed the properties of both parent cells. After fusion, the cytoplasm of the two cells was integrated, whereas their nuclei remained separate entities. Colocalization of MUC1 peptide and HLA-DR molecules was observed on fusion cells under the immunoelectron microscope. Coculture of patient-derived peripheral blood mononuclear cells (PBMC) with DC/tumor fusion cells resulted in activation of CD4 and CD8 T cells as assessed by IFN-gamma secretion, HLA-A*0201-MUC1 tetramer, and standard cytotoxic T lymphocyte (CTL) assays. The present study provides first evidence of integration of human DC and tumor cells and links their properties to T cell activation.
Koido
Shigeo
S
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Ohana
Masaya
M
Liu
Chunlei
C
Nikrui
Najmosama
N
Durfee
John
J
Lerner
Adam
A
Gong
Jianlin
J
D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002459:Cell Fusion; D048430:Cell Shape; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000941:Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins