Abstract IA23: Cervical tissue T cells in HPV disease.

Abstract

Abstract Despite the availability of preventative vaccines, human papillomaviruses (HPVs) cause more cancers than any other virus. Like other viral pathogens that cause human cancers, most HPV infections do not cause overt harm, let alone symptoms. Indeed, in immune-competent persons, most genital infections are eventually cleared. Nonetheless, the incidence of HPV-associated cancers in anatomic sites for which no screening algorithms have been validated is rising steadily. Preinvasive, intraepithelial lesions are associated with integration of the HPV genome into the host genome, and subsequent expression of the viral oncoproteins, E6 and E7, which are required for disease initiation and persistence. These true tumor-specific antigens provide non-“self” targets for immune therapies. The relatively indolent clinical course of preinvasive lesions, and tissue tropism of HPV infections provide opportunities to identify and treat early stage disease. In cervical HPV disease, a subset of high grade dysplastic lesions, cervical intraepithelial neoplasia grade 3 (CIN3), do in fact undergo complete regression, which is presumably immunologically mediated. However, T cell responses to viral antigens, measured in the blood, have not been informative with respect to immune responses in the cervical mucosa. Our team has been studying strategies to enhance the quality and magnitude of immune responses to HPV antigens. Ongoing clinical trials testing therapeutic vaccination and strategies to manipulate the lesion microenvironment to enhance homing and access of immune effector cells will be discussed. The design of these trials has been informed by studies of tissue-resident T cells in normal cervical mucosa, and by changes identified in dysplastic mucosa, both in lesions that regress, and in those that do not, in the course of a defined, prospective study window. Changes in the composition and distribution of tissue T cells postvaccination will be presented. Strategies to modify the stromal compartment of HPV lesions to promote lesion clearance will also be discussed. Citation Format: C.L. Trimble, J. Teague, T.C. Wu, R.A. Clark. Cervical tissue T cells in HPV disease. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA23.