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Innate direct anticancer effector function of human immature dendritic cells. II. Role of TNF, lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis-inducing ligand.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2002 Feb 15; Vol. 168 (4), pp. 1831-9. - Publication Year :
- 2002
-
Abstract
- Our recent studies have demonstrated that human immature dendritic cells (DCs) are able to directly and effectively mediate apoptotic killing against a wide array of cultured and freshly-isolated cancer cells without harming normal cells. In the present study, we demonstrate that this tumoricidal activity is mediated by multiple cytotoxic TNF family ligands. We determine that human immature DCs express on their cell surface four different cytotoxic TNF family ligands: TNF, lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis inducing ligand; while cancer cells express the corresponding death receptors. Disruptions of interactions between the four ligands expressed on DCs and corresponding death-signaling receptors expressed on cancer cells using specific Abs or R:Fc fusion proteins block the cytotoxic activity of DCs directed against cancer cells. The novel findings suggest that DC killing of cancer cells is mediated by the concerted engagement of four TNF family ligands of DCs with corresponding death receptors of cancer cells. Overall, our data demonstrate that DCs are fully equipped for an efficient direct apoptotic killing of cancer cells and suggest that this mechanism may play a critical role in both afferent and efferent anti-tumor immunity.
- Subjects :
- Apoptosis Regulatory Proteins
Cell Line
Cells, Cultured
Cytotoxicity Tests, Immunologic
Fas Ligand Protein
Humans
Lymphotoxin-alpha genetics
Lymphotoxin-alpha physiology
Lymphotoxin-beta
Membrane Glycoproteins genetics
Membrane Glycoproteins physiology
Membrane Proteins genetics
Membrane Proteins physiology
Microscopy, Confocal
Monocytes immunology
Neoplasms pathology
RNA, Messenger biosynthesis
Receptors, Tumor Necrosis Factor metabolism
Signal Transduction
Stem Cells immunology
TNF-Related Apoptosis-Inducing Ligand
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha physiology
Apoptosis
Dendritic Cells immunology
Neoplasms immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 168
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 11823516
- Full Text :
- https://doi.org/10.4049/jimmunol.168.4.1831