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

International Journal of Cancer. Journal International Du Cancer
Loane DecrausazDenise Nardelli-Haefliger

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 ...Continue Reading

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Citations

Oct 1, 2011·Drug Delivery and Translational Research·Jeremy S BlumW Mark Saltzman
Sep 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Todd BartkowiakMichael A Curran
Apr 9, 2016·Oncoimmunology·Shee Eun LeeJoon Haeng Rhee
Jul 4, 2015·Oncoimmunology·Sonia Domingos-PereiraDenise Nardelli-Haefliger
Jul 4, 2015·Cancer Immunology, Immunotherapy : CII·Aldo VenutiFrancesca Paolini
Jan 9, 2013·Human Vaccines & Immunotherapeutics·Francesca PaoliniAldo Venuti
Jun 22, 2012·Oncoimmunology·Denise Nardelli-HaefligerPatrice Jichlinski
Aug 21, 2013·The Journal of Urology·Sonia Domingos-PereiraDenise Nardelli-Haefliger
May 8, 2019·Journal for Immunotherapy of Cancer·Sonia Domingos-PereiraDenise Nardelli-Haefliger
Sep 15, 2020·Frontiers in Immunology·Samantha ZottnickAngelika B Riemer
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Jul 14, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Young Woo ChoiHyun-Tak Jin

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