Ovarian carcinoma expresses the NKG2D ligand Letal and promotes the survival and expansion of CD28- antitumor T cells.

Details

Serval ID
serval:BIB_B4BDED4CEB10
Type
Article: article from journal or magazin.
Collection
Publications
Title
Ovarian carcinoma expresses the NKG2D ligand Letal and promotes the survival and expansion of CD28- antitumor T cells.
Journal
Cancer Research
Author(s)
Conejo-Garcia J.R., Benencia F., Courreges M.C., Gimotty P.A., Khang E., Buckanovich R.J., Frauwirth K.A., Zhang L., Katsaros D., Thompson C.B., Levine B., Coukos G.
ISSN
0008-5472 (Print)
ISSN-L
0008-5472
Publication state
Published
Issued date
2004
Volume
64
Number
6
Pages
2175-2182
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Abstract
The role of the NKG2D immunoreceptor and its ligands in antitumor immune response is incompletely understood. Here, we report that effector immune cells infiltrating ovarian carcinoma are mostly CD8+ lymphocytes lacking CD28 but expressing the NKG2D costimulatory receptor. Human ovarian carcinoma expresses the novel NKG2D ligand lymphocyte effector cell toxicity-activating ligand (Letal). Letal was found to be an independent prognosticator of improved survival in advanced ovarian cancer. Higher levels of tumor-derived Letal were associated with stronger lymphocyte infiltration. Letal exerted marked costimulatory effects and induced type-1 polarization in CD8+CD28- tumor-infiltrating lymphocytes ex vivo. Letal engagement increased the expression of the glucose transporter Glut-1, enhanced glucose up-take, and protected CD8+ lymphocytes from cisplatin-induced killing. Letal also down-regulated the expression of Fas in CD8+ cells and rendered them resistant to Fas ligand-induced apoptosis. Our results indicate that Letal promotes tumor immune surveillance by promoting the survival and intratumoral expansion of antitumor cytotoxic lymphocytes. We propose that Letal could be used for the ex vivo expansion of apoptosis-resistant tumor-reactive cytotoxic lymphocytes for adoptive transfer.
Keywords
Adenocarcinoma, Mucinous/immunology, Adenocarcinoma, Mucinous/pathology, Animals, Antigens, CD28/metabolism, Apoptosis, CD8-Positive T-Lymphocytes/immunology, Carcinoma, Endometrioid/immunology, Carcinoma, Endometrioid/pathology, Cell Survival, Cystadenocarcinoma, Serous/immunology, Cystadenocarcinoma, Serous/pathology, Cytotoxicity, Immunologic, Female, Humans, Ligands, Lymphocyte Activation, Lymphocytes, Tumor-Infiltrating/immunology, Mice, Mice, Inbred C57BL, NK Cell Lectin-Like Receptor Subfamily K, Ovarian Neoplasms/immunology, Ovarian Neoplasms/pathology, Receptors, Immunologic/metabolism, Receptors, Natural Killer Cell
Pubmed
Web of science
Create date
14/10/2014 11:42
Last modification date
20/08/2019 15:23
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