Combination of lentivector immunization and low-dose chemotherapy or PD-1/PD-L1 blocking primes self-reactive T cells and induces anti-tumor immunity.

Détails

ID Serval
serval:BIB_CE29B7654AF2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Combination of lentivector immunization and low-dose chemotherapy or PD-1/PD-L1 blocking primes self-reactive T cells and induces anti-tumor immunity.
Périodique
European Journal of Immunology
Auteur(s)
Sierro S.R., Donda A., Perret R., Guillaume P., Yagita H., Levy F., Romero P.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Statut éditorial
Publié
Date de publication
2011
Volume
41
Numéro
8
Pages
2217-2228
Langue
anglais
Résumé
In the last two decades, anti-cancer vaccines have yielded disappointing clinical results despite the fact that high numbers of self/tumor-specific T cells can be elicited in immunized patients. Understanding the reasons behind this lack of efficacy is critical in order to design better treatment regimes. Recombinant lentivectors (rLVs) have been successfully used to induce antigen-specific T cells to foreign or mutated tumor antigens. Here, we show that rLV expressing a murine nonmutated self/tumor antigen efficiently primes large numbers of self/tumor-specific CD8(+) T cells. In spite of the large number of tumor-specific T cells, however, no anti-tumor activity could be measured in a therapeutic setting, in mice vaccinated with rLV. Accumulating evidence shows that, in the presence of malignancies, inhibition of T-cell activity may predominate overstimulation. Analysis of tumor-infiltrating lymphocytes revealed that specific anti-tumor CD8(+) T cells fail to produce cytokines and express high levels of inhibitory receptors such as programmed death (PD)-1. Association of active immunization with chemotherapy or antibodies that block inhibitory pathways often leads to better anti-tumor effects. We show here that combining rLV vaccination with either cyclophosphamide or PD-1 and PD-L1 blocking antibodies enhances rLV vaccination efficacy and improves anti-tumor immunity.
Mots-clé
Animals, Antibodies, Blocking/immunology, Antibodies, Blocking/pharmacology, Antigens, CD80/immunology, Antigens, Differentiation/immunology, Antineoplastic Agents/pharmacology, Cell Line, Tumor, Combined Modality Therapy, Cyclophosphamide/pharmacology, Dose-Response Relationship, Drug, Epitopes/immunology, Genetic Vectors/genetics, Genetic Vectors/metabolism, Green Fluorescent Proteins/genetics, Green Fluorescent Proteins/metabolism, Immunization/methods, Interferon-gamma/immunology, Interferon-gamma/metabolism, Intramolecular Oxidoreductases/immunology, Lentivirus/genetics, Lentivirus/immunology, Lymphocyte Count, Melanoma, Experimental/drug therapy, Melanoma, Experimental/immunology, Membrane Glycoproteins/immunology, Mice, Mice, Inbred C57BL, Peptides/immunology, Signal Transduction/drug effects, Signal Transduction/immunology, T-Lymphocytes/drug effects, T-Lymphocytes/immunology, Treatment Outcome, Tumor Necrosis Factor-alpha/immunology, Tumor Necrosis Factor-alpha/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/08/2011 11:13
Dernière modification de la notice
20/08/2019 16:48
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