PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8⁺ T cells induced by melanoma vaccines.

Détails

Ressource 1Télécharger: BIB_C8D0A16139EF.P001.pdf (3775.57 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_C8D0A16139EF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8⁺ T cells induced by melanoma vaccines.
Périodique
Cancer Research
Auteur(s)
Fourcade J., Sun Z., Pagliano O., Chauvin J.M., Sander C., Janjic B., Tarhini A.A., Tawbi H.A., Kirkwood J.M., Moschos S., Wang H., Guillaume P., Luescher I.F., Krieg A., Anderson A.C., Kuchroo V.K., Zarour H.M.
ISSN
1538-7445 (Electronic)
ISSN-L
0008-5472
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
74
Numéro
4
Pages
1045-1055
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Although melanoma vaccines stimulate tumor antigen-specific CD8(+) T cells, objective clinical responses are rarely observed. To investigate this discrepancy, we evaluated the character of vaccine-induced CD8(+) T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. The vaccines included incomplete Freund's adjuvant, CpG oligodeoxynucleotide (CpG), and the HLA-A2-restricted analog peptide NY-ESO-1 157-165V, either by itself or in combination with the pan-DR epitope NY-ESO-1 119-143. Both vaccines stimulated rapid tumor antigen-specific CD8(+) T-cell responses detected ex vivo, however, tumor antigen-specific CD8(+) T cells produced more IFN-γ and exhibited higher lytic function upon immunization with MHC class I and class II epitopes. Notably, the vast majority of vaccine-induced CD8(+) T cells upregulated PD-1 and a minority also upregulated Tim-3. Levels of PD-1 and Tim-3 expression by vaccine-induced CD8(+) T cells at the time of vaccine administration correlated inversely with their expansion in vivo. Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8(+) T cells in vitro. Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma.
Pubmed
Web of science
Open Access
Oui
Création de la notice
21/04/2014 16:48
Dernière modification de la notice
20/08/2019 16:43
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