Investigation On Loss Of TAP And HLA-A2 In Tumor Tissues Of RCC And TCC And Its Impacts On Cellula Immunity

The MHC class I antigen processing and presentation machinery, which play a key role in the defense viruses and tumors. In some human tumors, reduced or defective MHC class I surface expression has been attributed to functional deficiencies of the antigen-processing molecules, the proteasome subunits low molecular weight(LMP)-2, LMP-7, the peptide transporters associated with antigen processing(TAP)l,TAP2, as well as the HLA-I themselves. In human tumor of distinct histology, changes in the expression of these processing molecules were frequently found, such as melanoma, breast cancer, cervix cancer and so on, which prevented from presenting of TAA. It may provide malignant tumor cells with mechanisms to escape from T-cell recognition and destruction. The most common human MHC class I molecule is HLA-A2, which is found at high frequency in most population. Clarifying the expression and effect of MHC class I antigen-processing molecules will conduce to immunotherapy for tumor patients, it may provid us a new way.Using specimens of RCC and TCC patients admitted to our hospital, we investigated whether the loss or reducing of TAP protein and HLA-A2 mRNA occurs in this kind of tumor by means of immunohistochemistry and reverse transcription polymerase chain reaction.The results from experiment I indicated that the TAP expression was reduced or defective in RCC and TCC, when compared to the corresponding normal tissue. In RCC. the loss value of TAP is 100%, almost completely negative. With theprogression of tumor stage and grade, the decreased level is slightly different, but the difference is not statistically significant. In TCC of bladder, the loss of TAP is mainly partial. Expression in high grade and invasive tumors is decreased than low grade and superficial tumors. In two groups of case, the reduced level of TAP 1 and TAP2 is almost coincident, it is more serious in RCC than TCC.The results from experiment II indicated that 2 cases of all are negative of HLA-A2 in RCC, the level of HLA-A2 mRNA in tumor is lower than normal control tissue in HLA-A2+ patients. With the progression of tumor stage and grade, the HLA-A2 expression decreased, tumor in T3/T2 and high grade is lower than Tl and low grade, the difference is statistically significant, but the difference between T2 and T3 is not statistically significant. In TCC of bladder, the similar result was found. 2 cases of all are negative of HLA-A2. the level of HLA-A2 mRNA in tumor is lower than normal control tissue. With the progression of tumor stage and grade, the HLA-A2 expression decreased, the difference is statistically significant in different groups.