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-gamma.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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


RESULTS
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.


CONCLUSIONS
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.
Sikorski
Marek
M
Genix Medical Centre, Lublin, Poland.
Bobek
Malgorzata
M
Zrubek
HenryK
H
Marcinkiewicz
Janusz
J
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D001707:Biopsy, Needle; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000008:administration & dosage*; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis*; D011336:Probability; D011446:Prospective Studies; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D014408:Biomarkers, Tumor; D004279:DNA, Viral; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D007371:Interferon-gamma