A novel mucosal orthotopic murine model of human papillomavirus-associated genital cancers.

Details

Serval ID
serval:BIB_AF6C31E8EF7B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A novel mucosal orthotopic murine model of human papillomavirus-associated genital cancers.
Journal
International Journal of Cancer. Journal International Du Cancer
Author(s)
Decrausaz L., Gonçalves A.R., Domingos-Pereira S., Pythoud C., Stehle J.C., Schiller J., Jichlinski P., Nardelli-Haefliger D.
ISSN
1097-0215 (Electronic)
ISSN-L
0020-7136
Publication state
Published
Issued date
2011
Volume
128
Number
9
Pages
2105-2113
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Cervical cancer results from infection with high-risk type human papillomaviruses (HPV). Therapeutic vaccines aiming at controlling existing genital HPV infections and associated lesions are usually tested in mice with HPV-expressing tumor cells subcutaneously implanted into their flank. However, effective vaccine-induced regression of these ectopic tumors strongly contrasts with the poor clinical results of these vaccines produced in patients with HPV-associated genital neoplasia. To assess HPV therapeutic vaccines in a more relevant setting, we have, here, established an orthotopic mouse model where tumors in the genital mucosa (GM) develop after an intravaginal instillation of HPV16 E6/E7-expressing tumor cells transduced with a luciferase-encoding lentiviral vector for in vivo imaging of tumor growth. Tumor take was 80-90% after nonoxynol-9 induced damage of the epithelium. Tumors remained localized in the genital tract, and histological analysis showed that most tumors grew within the squamous epithelium of the vaginal wall. Those tumors induced (i) E7-specific CD8 T cells restricted to the GM and draining lymph nodes, in agreement with their mucosal location and (ii) high Foxp3+ CD4+ infiltrates, similarly to those found in natural non-regressing HPV lesions. This novel genital HPV-tumor model by requiring GM homing of vaccine-induced immune responses able to overcome local immuno-suppression may be more representative of the situation occurring in patients upon therapeutic vaccination.
Keywords
Animals, Carcinoma, Squamous Cell/immunology, Carcinoma, Squamous Cell/pathology, Disease Models, Animal, Female, Humans, Immunohistochemistry, Mice, Mice, Inbred C57BL, Neoplasm Transplantation/immunology, Neoplasm Transplantation/methods, Papillomavirus Infections/complications, Transplantation, Heterologous/immunology, Transplantation, Heterologous/methods, Uterine Cervical Neoplasms/immunology, Uterine Cervical Neoplasms/pathology
Pubmed
Web of science
Open Access
Yes
Create date
17/08/2010 13:34
Last modification date
20/08/2019 16:18
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