TRANCE- and CD40 ligand-matured dendritic cells reveal MHC class I-restricted T cells specific for autologous tumor in late-stage ovarian cancer patients.

Détails

ID Serval
serval:BIB_A87E75B72F36
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TRANCE- and CD40 ligand-matured dendritic cells reveal MHC class I-restricted T cells specific for autologous tumor in late-stage ovarian cancer patients.
Périodique
Clinical Cancer Research
Auteur⸱e⸱s
Schlienger K., Chu C.S., Woo E.Y., Rivers P.M., Toll A.J., Hudson B., Maus M.V., Riley J.L., Choi Y., Coukos G., Kaiser L.R., Rubin S.C., Levine B.L., Carroll R.G., June C.H.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Statut éditorial
Publié
Date de publication
2003
Volume
9
Numéro
4
Pages
1517-1527
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
PURPOSE: The use of mature dendritic cells (DCs) presenting tumor-associated antigens (TAAs) to trigger tumor-specific T cells in vivo or in vitro represents a promising approach for cancer immunotherapy. We hypothesized that tumor antigens, mostly unidentified, are present on ovarian tumor cells and that mature DCs could be used to generate tumor-specific responses in unprimed patients. We also sought to measure preexisting antitumor immunity in patients with advanced ovarian cancer.
EXPERIMENTAL DESIGN: Autologous DCs from 10 patients with ovarian cancer were pulsed with killed autologous primary tumors as a source of TAAs. DCs were then cultured in the presence of tumor necrosis factor alpha + TRANCE (tumor necrosis factor-related activation-induced cytokine) to induce maturation. Mature TAA-pulsed DCs were used in vitro to stimulate tumor-specific peripheral blood T cells.
RESULTS: TRANCE and CD40 ligand were effective at maturing DCs. T-cell lines were generated in vitro that were capable of secreting IFN-gamma in response to autologous tumor. These tumor-specific T cells were MHC class I restricted. The frequency of tumor-specific T cells in uncultured cells from malignant ascites fluid and peripheral blood was measured in the same patients.
CONCLUSIONS: IFN-gamma-secreting tumor-specific T cells were demonstrated at baseline in uncultured T cells from some unvaccinated ovarian cancer patients; however, the T cells could not kill autologous tumor. These data demonstrate that mature DCs presenting tumor antigens from engulfed autologous tumors can be used to augment antitumor immunity in vitro in patients with epithelial ovarian cancer. The results support the feasibility of therapeutic vaccination of ovarian cancer patients.
Mots-clé
Adult, Aged, Apoptosis, CD40 Ligand/metabolism, Cancer Vaccines, Carrier Proteins/metabolism, Cell Death, Cell Line, Tumor, Dendritic Cells/metabolism, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Genes, MHC Class I/genetics, Humans, Immunotherapy/methods, Interferon-gamma/metabolism, Leukocytes, Mononuclear/metabolism, Male, Membrane Glycoproteins/metabolism, Middle Aged, Ovarian Neoplasms/immunology, Ovarian Neoplasms/metabolism, Phagocytosis, Phenotype, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, T-Lymphocytes/metabolism, Ultraviolet Rays
Pubmed
Web of science
Création de la notice
14/10/2014 11:43
Dernière modification de la notice
20/08/2019 15:12
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