EFFECTS OF RETINOIC ACID COMBINED WITH INTERFERON-GAMMA ON THE EXPRESSION OF MAJOR-HISTOCOMPATIBILITY-COMPLEX MOLECULES AND INTERCELLULAR-ADHESION MOLECULE-1 HUMAN CERVICAL-CANCER

Retinoids and interferons are important regulators of human epithelial cell differentiation and have been successfully used in the clinical treatment of HPV-involved cervical cancer, In this study, 2 HPV-positi ve human cervical-carcinoma cell lines were analyzed for their surface expression of MHC-Class-I, MHC-Class-II and ICAM-1 surface antigens b efore and after exposure to all-trans retinoic acid, interferon-gamma and the combination of the 2 compounds, In addition, the effects on HL A-Class-I-mRNA expression were evaluated after such treatments, Both c ell lines expressed MHC-Class-I molecules, and their levels were marke dly up-regulated after exposure to IFN-gamma. Similarly, MHC-Class-II and ICAM-1 antigens were either induced or significantly up-regulated by IFN-gamma., Exposure to ail-trans retinoic acid was also able to si gnificantly increase the expression of MHC-Class-I and ICAM-1 antigens as compared with untreated tumor cells, However, unlike IFN-gamma, re tinoids were not able to induce the expression of HLA-Class-II surface antigens. Exposure to the combination of IFN-gamma plus retinoic acid significantly up-regulated (in an additive manner) HLA-Class-I and IC AM-1 molecules as compared with the levels obtainable after exposure t o IFN-gamma alone, Finally, Northern-blot analysis of HLA-Class-I-mRNA expression confirmed that the activity of both of these biologic resp onse modifiers was at transcriptional level. These data indicate that the combination of these modalities could induce an additive effect on the expression of immunologically important surface antigens on human cervical-cancer cells. These findings, together with the known anti-p roliferative effects mediated by retinoids and IFN-gamma on tumor cell s, further support the combination of these agents in the treatment of pre-invasive and invasive human cervical cancer. (C) 1998 Wiley-Liss, Inc.