Fiche publication
Date publication
septembre 2018
Journal
International journal of cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier
,
Dr MANSI Laura
Tous les auteurs :
Beziaud L, Boullerot L, Tran T, Mansi L, Marie-Joseph EL, Ravel P, Johannes L, Bayry J, Tartour E, Adotévi O
Lien Pubmed
Résumé
mTOR pathway inhibitors such as rapalogs represent a promising tool to induce functional memory CD8 T cells. In this study, we investigated the combination of temsirolimus with anticancer vaccines. Using various designs of cancer vaccines (short and long peptides or the B subunit of Shiga toxin as an antigen delivery vector) and tumor models (melanoma, lung and colon cancer), we showed that the administration of temsirolimus efficiently decreased tumor growth and enhanced tumor-specific CD8 T-cell responses induced by vaccination. Furthermore, tumor-specific CD8 T cells induced by the bi-therapy (vaccine + temsirolimus) exhibit phenotypic characteristics of central memory (CD127 CD62L ) CD8 T cells compared to vaccination alone. We demonstrated that regulatory CD4 T cells (T ) expansion in vivo limits the efficacy of the bi-therapy by altering the antitumor CD8 T-cell responses. Finally, the use of a small molecule CCR4 antagonist to prevent T induction considerably improved the efficacy of the bi-therapy by enhancing CD8 T cells-mediated antitumor immunity. Taken together, this study highlights the potential interest of combining cancer vaccines with drugs that promote memory CD8 T cells and inhibit T . This article is protected by copyright. All rights reserved.
Mots clés
CCR4 antagonist, CD8 T cells, cancer vaccine, rapalog, regulatory CD4 T cells
Référence
Int. J. Cancer. 2018 Sep 5;:
