Herpes virus oncolytic therapy reverses tumor immune dysfunction and facilitates tumor antigen presentation.

Détails

ID Serval
serval:BIB_CA92EFBA1EDC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Herpes virus oncolytic therapy reverses tumor immune dysfunction and facilitates tumor antigen presentation.
Périodique
Cancer Biology and Therapy
Auteur(s)
Benencia F., Courrèges M.C., Fraser N.W., Coukos G.
ISSN
1555-8576 (Electronic)
ISSN-L
1538-4047
Statut éditorial
Publié
Date de publication
2008
Volume
7
Numéro
8
Pages
1194-1205
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., ExtramuralPublication Status: ppublish
Résumé
We have previously shown that intratumor administration of HSV-1716 (an ICP34.5 null mutant) resulted in significant reduction of tumor growth and a significant survival advantage in a murine model of ovarian cancer. Herewith we report that oncolytic HSV-1716 generates vaccination effects in the same model. Upon HSV-1716 infection, mouse ovarian tumor cells showed high levels of expression viral glycoproteins B and D and were highly phagocyted by dendritic cells (DCs). Interestingly, increased phagocytosis of tumor-infected cells by DCs was impaired by heparin, and anti-HSV glycoproteins B and D, indicating that viral infection enhances adhesive interactions between DCs and tumor apoptotic bodies. Moreover, HSV-1716 infected cells expressed high levels of heat shock proteins 70 and GRP94, molecules that have been reported to induce maturation of DCs, increase cross-presentation of antigens and promote antitumor immune response. After phagocytosis of tumor-infected cells, DCs acquired a mature status in vitro and in vivo, upregulated the expression of costimulatory molecule and increased migration towards MIP-3beta. Furthermore, HSV-1716 oncolytic treatment markedly reduced vascular endothelial growth factor (VEGF) levels in tumor-bearing animals thus abrogating tumor immunosuppressive milieu. These mechanisms may account for the highly enhanced antitumoral immune responses observed in HSV-1716 treated animals. Oncolytic treatment induced a significantly higher frequency of tumor-reactive IFNgamma producing cells, and induced a robust tumor infiltration by T cells. These results indicate that oncolytic therapy with HSV-1716 facilitates antitumor immune responses.
Mots-clé
Animals, Antigen Presentation/genetics, Antigen Presentation/immunology, Antigens, Neoplasm/genetics, Antigens, Neoplasm/immunology, Female, Immunohistochemistry, Mice, Mice, Inbred C57BL, Neoplasms/immunology, Neoplasms/therapy, Oncolytic Virotherapy/methods, Ovarian Neoplasms/immunology, Ovarian Neoplasms/therapy, Simplexvirus/genetics, Simplexvirus/immunology, Tumor Cells, Cultured
Pubmed
Web of science
Création de la notice
14/10/2014 12:42
Dernière modification de la notice
20/08/2019 16:45
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