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

Details

Serval ID
serval:BIB_CA92EFBA1EDC
Type
Article: article from journal or magazin.
Collection
Publications
Title
Herpes virus oncolytic therapy reverses tumor immune dysfunction and facilitates tumor antigen presentation.
Journal
Cancer Biology and Therapy
Author(s)
Benencia F., Courrèges M.C., Fraser N.W., Coukos G.
ISSN
1555-8576 (Electronic)
ISSN-L
1538-4047
Publication state
Published
Issued date
2008
Volume
7
Number
8
Pages
1194-1205
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., ExtramuralPublication Status: ppublish
Abstract
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.
Keywords
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
Create date
14/10/2014 11:42
Last modification date
20/08/2019 15:45
Usage data