Investigation Of Aberrant HLA Molecules Expression In Oral Squamous Carcinoma And Its Mechanism

To investigate whether HLA molecules expression downregulated in OSCC or not and the primary mechanism underling this downregulation, we investigate HLA molecules expression of tissue in vivo and of corresponding cell lines cultured in vitro. Using a panel of antibodies, the expression of HLA class I molecules was studied by immunohistochemical technique, flow cytometer and semiquantitative western blot assay. To better characterize the HLA molecules downregulation, we also extended this analysis to RNA level by RT-PCR with specific primers. The result showed that on tissue level, the percentage of downregulation of HLA class I heavy-chain (B/C locus and A2 locus),β2m and LMP2 was 31%,55%,35% and 43% respectively; In comparison with normal epithelial cell line (Hacat), the expression of HLA class I antigens of OSCC cell lines were also reduced by flow cytometry and western blot assay; and two OSCC cell lines all showed diminished expression of A,B,C, LMP7, LMP10 transcripts, further, the LMP2, PA28βtranscripts of KB were almost undetectable. Our results indicate that HLA class I antigen expression downregulated in OSCC tissue and cell lines .The data based on cell lines shows that the downregulation presumably mainly due to low efficiency of HLA genes transcription; other reasons such as defect in the expression of LMP molecules, abnormality of post-transcription regulation may also play a role. The abnormality may provide tumor cells with a mechanism to escape from immune recognition and enhance their metastatic potential.