Published online Oct 10, 2014. doi: 10.5306/wjco.v5.i4.753
Revised: April 5, 2014
Accepted: May 16, 2014
Published online: October 10, 2014
Processing time: 216 Days and 3 Hours
Cervical cancer is a worldwide disease that constitutes a significant public health problem, especially in developing countries, not only due to its high incidence but also because the most affected population comprises women who belong to marginalized socio-economic classes. Clinical and molecular research has identified immunological impairment in squamous intraepithelial cervical lesions and cervical cancer patients. Human Papillomavirus (HPV) has several mechanisms for avoiding the immune system: it down-regulates the expression of interferon and upregulates interleukin (IL)-10 and transforming growth factor (TGF)-β1 to produce a local immunosuppressive environment, which, along with altered tumor surface antigens, forms an immunosuppressive network that inhibits the antitumor immune response. In this review we analyzed the available data on several deregulated cellular immune functions in patients with NIC I, NIC II and NIC III and cervical cancer. The effects of immunosuppressive cytokines on innate immune response, T-cell activation and cellular factors that promote tumor cell proliferation in cervical cancer patients are summarized. We discuss the functional consequences of HPV E2, E6, and E7 protein interactions with IL-10 and TGF-β1 promoters in the induction of these cytokines and postulate its effect on the cellular immune response in squamous intraepithelial cervical lesions and cervical cancer patients. This review provides a comprehensive picture of the immunological functions of IL-10 and TGF-β1 in response to HPV in humans.
Core tip: Human Papillomavirus (HPV) persistence is a key event for cervical cancer development. HPV proteins E2, E6 and E7 induce the transcription of immunosuppressive cytokines as a means of evading HPV the host immune system. We postulate that interleukin-10 and transforming growth factor-β1 induce HPV immune system evasion through an immunosuppressive state in the local microenvironment of the cervix in HPV-infected women. These findings allow us to gain insight in our understanding of how HPV persist in the cervix and favor cervical lesions and cancer development, with potentially strong impact on vaccine development and the design of new targeted immunotherapies for women with cervical neoplasia.