Letal, A tumor-associated NKG2D immunoreceptor ligand, induces activation and expansion of effector immune cells.

Details

Serval ID
serval:BIB_9C5055888273
Type
Article: article from journal or magazin.
Collection
Publications
Title
Letal, A tumor-associated NKG2D immunoreceptor ligand, induces activation and expansion of effector immune cells.
Journal
Cancer Biology and Therapy
Author(s)
Conejo-Garcia J.R., Benencia F., Courreges M.C., Khang E., Zhang L., Mohamed-Hadley A., Vinocur J.M., Buckanovich R.J., Thompson C.B., Levine B., Coukos G.
ISSN
1538-4047 (Print)
ISSN-L
1538-4047
Publication state
Published
Issued date
2003
Volume
2
Number
4
Pages
446-451
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Abstract
NKG2D serves as one of the most potent activating receptors for effector lymphocytes. in peripheral tissues. Here we report the characterization of Letal, the first human trans-membrane NKG2D ligand lacking an immunoglobulin-like alpha-3 ectodomain. Letal is constitutively expressed by a variety of normal tissues, and is upregulated in tumor cells of different origins. Unlike other NKG2D ligands, Letal mRNA expression progressively decreased after treatment of tumor cells with retinoic acid. Simultaneous T-cell receptor activation and engagement of Letal stimulated proliferation of CD8(+) cells and dramatically increased IL-2 and IFNgamma secretion. In addition, Letal induced the killing of cancer cells by CD8(+) and NK cells. These results suggest that Letal delivers activating signals to NK cells and promotes tumor immune surveillance by inducing the expansion of anti-tumor cytotoxic lymphocytes.
Keywords
Amino Acid Sequence, Animals, Apoptosis/drug effects, CD8-Positive T-Lymphocytes/immunology, Colonic Neoplasms/drug therapy, Colonic Neoplasms/immunology, Cytotoxicity, Immunologic, Female, Humans, Immunoglobulin G/immunology, Interferon-gamma/metabolism, Interleukin-2/metabolism, K562 Cells, Killer Cells, Natural/immunology, Killer Cells, Natural/metabolism, Ligands, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Molecular Sequence Data, NK Cell Lectin-Like Receptor Subfamily K, Ovarian Neoplasms/drug therapy, Ovarian Neoplasms/immunology, RNA, Messenger/metabolism, Receptors, Antigen, T-Cell/metabolism, Receptors, Immunologic/genetics, Receptors, Immunologic/metabolism, Receptors, Natural Killer Cell, Sequence Homology, Amino Acid, Tretinoin/therapeutic use, Type C Phospholipases/pharmacology
Pubmed
Web of science
Create date
14/10/2014 11:43
Last modification date
20/08/2019 15:03
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