MHC CLASS-I AND CLASS-II EXPRESSION IN PROSTATE CARCINOMA AND MODULATION BY INTERFERON-ALPHA AND INTERFERON-GAMMA

BACKGROUND. Expression of Major Histocompatibility Complex (MHC) class I and II antigens are critical for the cellular immune response. Loss of MHC expression represents one mechanism by which cancer cells esca pe immune recognition. PURPOSE. To define MHC class I and II expressio n by prostate cancer (PCa) in vivo and in vitro and the ability to mod ulate MHC expression in vitro with IFN-alpha and -gamma. METHODS. Froz en tissue sections of 25 benign prostatic hyperplasia (BPH) and 18 PCa specimens were studied by immunohistochemistry. PCa cell Lines LNCaP, PC-3, and DU145 were studied by FAGS, ELISA, and cytospin. Class I wa s detected by monoclonal antibody (mAb) W6/32, and class II by mAb 13. 17. The effects of IFN-alpha and gamma were assessed by testing the th ree cell lines in the presence or absence of varying concentrations of the cytokine for varying incubation times. RESULTS. Class I was stron gly expressed by 24/25 BPH specimens; 4/18 (22%) PCa were homogeneousl y class I-positive, while 5/18 (28%) were heterogeneously positive and 9/18 (50%) were class I-negative. PC-3 and DU-145 expressed normal le vels of class I, while LNCaP expressed only low levels. All lines exce pt LNCaP demonstrated significant up-regulation of class I with either IFN-alpha or -gamma. Class II expression was not seen in BPH epitheli um nor in 17/18 PCa. Class II could be only weakly induced in the thre e PCa lines. CONCLUSIONS. These findings confirm prior studies demonst rating that class I expression is commonly lost or diminished in PCa. In addition, class II up-regulation by IFN-gamma appears very limited in relation to other normal or neoplastic epithelium. IMPLICATIONS. Th e present findings, taken together with previous studies, are most con sistent with the expression of neoantigens by PCa, which are recognize d and appropriately eliminated by the cellular immune system. This sel ective pressure favors outgrowth of cells which down-regulate or lose class I and/or class II expression. Understanding PCa immunobiology wi ll help in the development of effective immunotherapy for this disease . (C) 1997 Wiley-Liss, Inc.