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Cervical Cancer-Associated Human Papillomavirus 16 E7 Oncoprotein Inhibits Induction of Anti-Cancer Immunity by a CD4+ T Cell Dependent Mechanism

Marion E. G. Brunck¹, Xiao Song Liu², Jie Zhong³ & Germain J. Fernando¹

Correspondence: (Login to view email address)

1. The University of Queensland
2. Mater Medical Research Institute, Brisbane
3. Queensland Institute of Medical Research, Brisbane

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Document Type:

Manuscript

Date:

Received 07 July 2009 04:20 UTC; Posted 08 July 2009

Subjects:

Cancer, Immunology

Tags:

• HPV
• cervical cancer
• oncogene
• immunotherapy
• Immune Evasion
• Vaccine

Abstract:

Attempts to develop therapeutic vaccines against cervical cancer have been proven difficult. One of the major causes of the failure is due to the use of the wrong mouse models based on transplantable tumours in testing the efficacy of vaccines. Now that a transgenic epithelial mouse model has been developed to closely mimic cervical cancer, the mechanisms needed to eliminate this type of cancer could be studied. The E7 oncoprotein of Human Papillomavirus (HPV) is the most expressed HPV protein in cervical cancers and its continuous production is essential to maintain the cancerous state and therefore the obvious target in the development of vaccines. Skin grafts expressing the HPV 16 E7 protein (E7 autografts) are not spontaneously rejected from an MHC matched immunocompetent host. Interestingly, simultaneous placement of an MHC mismatched skin (allograft) next to an E7 autograft results in the E7 autograft rejection. However when the allograft also expresses E7, the E7 autograft is rejected more slowly. Autograft rejection requires CD8+ T cells, and is accelerated by removal of CD4+ T cells after placement of the E7 expressing allograft, suggesting induction of an E7 specific CD4+ regulatory T cell population by the E7 expressing allograft. This observation may have implications in designing effective vaccines and immunotherapy against cervical cancers in women.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Brunck, Marion, Liu, Xiao Song, Zhong, Jie, and Fernando, Germain. Cervical Cancer-Associated Human Papillomavirus 16 E7 Oncoprotein Inhibits Induction of Anti-Cancer Immunity by a CD4+ T Cell Dependent Mechanism . Available from Nature Precedings <http://dx.doi.org/10.1038/npre.2009.3405.1> (2009)

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