RETINOIC ACID UP-REGULATES THE EXPRESSION OF MAJOR HISTOCOMPATIBILITYCOMPLEX-MOLECULES AND ADHESION COSTIMULATION MOLECULES (SPECIFICALLY,INTERCELLULAR-ADHESION MOLECULE ICAM-1) IN HUMAN CERVICAL-CANCER/

OBJECTIVE: Retinoids are a class of compounds that are structurally re lated to vitamin A and have been found to be effective in the preventi on and treatment of cervical cancer. To investigate whether enhanced i mmunogenicity might be responsible for such efficacy, we evaluated the effects of retinoic acid on the expression of major histocompatibilit y complex class I and class II and intercellular adhesion molecule ICA M-1 in human cervical carcinoma cell lines. STUDY DESIGN: The expressi on of surface antigens (major histocompatibility complex class I and c lass II and ICAM-1) was evaluated by fluorescence-activated cell sorte r analysis in 3 human cervical carcinoma cell lines after exposure to therapeutic doses of retinoic acid. In addition, the effects on human leukocyte antigen class I messenger ribonucleic acid expression were a lso evaluated by Northern blot analysis after such treatment. RESULTS: CaSki, SiHa, and HT-3 cervical cancer cells expressed variable levels of major histocompatibility complex class I and ICAM-1 antigens, wher eas class Ii surface antigens were not detectable. Exposure to therape utic doses of retinoic acid were able to significantly increase the ex pression of major histocompatibility complex class I and ICAM-1 antige ns in all the cell lines when compared with untreated tumor cells but were not able to induce the expression of class II surface human leuko cyte antigens. Northern blot analysis showed that for major histocompa tibility complex class I molecules such up-regulation was the result o f an increased expression at the transcriptional level of major histoc ompatibility complex class I messenger ribonucleic acid. CONCLUSIONS: These data indicate that retinoic acid increases the expression of imm unologically important surface antigens, suggesting that the efficacy of retinoic acid in the treatment of cervical cancer may be, at least in part, the result of immunologic modulation. Such findings support a dditional clinical research investigating the use of retinoids for the treatment of cervical cancer.