Dynamics of selected MHC class I and II molecule expression in the course of HPV positive CIN treatment with the use of human recombinant IFN‐γ

Abstract

Studies consistently reveal downregulation of major histocompatibility complex (MHC)-I molecules or/and selective loss of individual MHC-I alleles and upregulation of MHC-II molecules in the areas of cervical intraepithelial neoplasia (CIN) and in cervical cancers. In vitro studies demonstrated the interferon-gamma (IFN-gamma) potential of MHC class I and II molecule upregulation followed by increased cytolytic response against some cervical cancer cell lines. In vivo assessment of the correlation between regression/persistence state of CIN and the IFN-gamma-induced changes in both class of selected MHC molecule expression. Seventeen subjects with CIN I/CIN II associated with high-risk HPV infection underwent uniform IFN-gamma treatment (four intracervical injections over 2-day interval for a total dose of 6,000,000 IU). Immunohistochemical staining has been performed within cervical punch biopsy specimens with the use of monoclonal antibody reacting with HLA-DR, HLA-HC and HLA-Bw4, and the mean proportion of given molecules expressing keratinocytes was counted before, immediately after and 2 months after IFN-gamma treatment The analysis revealed a rapid and significant increase of the HLA-Bw4 proportion in response to IFN-gamma, persistent in the group of complete responders (with CIN clearance). No significant changes in the proportion of HLA-HC 10 positive cells in response to IFN-gamma administration was demonstrated, nor a significant increase in HLA-DR positivity; however, the transient trend towards increasing the proportion of HLA-DR immediately after treatment completion was observed. Upregulation of selected MHC class I allele expression, but not necessary MHC class II or heavy chain fragments of MHC-I, induced by IFN-gamma correlates with the resolution of cervical intraepithelial lesions and high-risk HPV DNA clearance in vivo.