Comparative assessment of MHC antigen expression in bladder and testis tumour biopsies and established urological tumour cell lines: The relevance ofcytokine and gene transfection for correction of defective MHC antigens

The aim of this study using radio-binding (RB), peroxidase-anti-peroxidase (PAP) and immunoprecipitation (IP) techniques was to investigate the patter n of major histocompatibility complex (MHC) antigen expression in urologica l malignancies and to compare the results with those seen in established ur ological human tumour cell lines. The results showed that using PAP techniq ue, the percent bladder cases showing complete loss or cases with greater t han 90% of tumour cells negative with W6/32 (detects all class I antigens), HC10 (detects free heavy chain) and BMM.1 (detects beta 2-mirogobulin) mon oclonal antibodies (Mab) were 16%, 44% and 2% respectively. In a subgroup o f 37 cases, the intensity of MHC class II antigen expression for strong, we ak and negative cases were 9 (24%), 8 (22%) and 20 (54%) respectively. The expression for class I antigens on testis tumours was mainly negative and w hen positive, it was present in a small percent of tumour cells. This was a lso observed for class II antigens where only 8% of cases showed some degre e of positivity. Using RE technique, 10 of 12 (85%) of tumour lines express ed class I antigens spontaneously and following interferon gamma (IFN gamma ) stimulation, the 2 negative lines one testis (Tera I) and one bladder (Fe n) remained negative and 2 lines (both testis lines Tera II and Ep2102) sho wed a significant class I up-regulation. None of the lines expressed class II antigens spontaneously and following IFN gamma stimulation, 8 of 12 (66% ) were induced. The absence of class I and II antigens in the negative line s was confirmed using IP technique. In the case of one class I negative bla dder cell line i.e. Fen, the biochemical analysis showed the absence of bet a 2-m gene product which could not be restored by IFN gamma stimulation. Ho wever, transfection of the cells with beta 2-m gene resulted in the express ion of fully assembled class I antigens, indicating that the loss of antige ns was due to the absence of functional beta 2-m gene. These results indica ted the similarity between the pattern of expression of MHC antigens on tum our biopsies and established tumour cell lines. They also demonstrated that both cytokine stimulation and gene transfection could be used to correct d efective class I antigens in tumour cell lines. These approaches might have important implications for preselection of bladder cancer patients for cyt okine or gene therapies.