The human leucocyte antigen complex: its role in colorectal cancer

The human leucocyte antigen (HLA) is frequently altered in human tumours compared to the tissue from which they originate. The ability of the tumour to invade requires a change in the phenotype of the cell allowing it to advance and expand without restraint from adjacent tissue and the host immune system. One important regulator of tumour growth is cellular immunity. Antigen recognition by "T" cells occurs in the context of the HLA products. Changes in the HLA expression of a malignant tissue may directly influence immunosurveillance mechanisms, as these molecules play a central role in presenting potentially immunogenic peptides to "T" cells. To assess whether alteration in HLA expression is a critical step in the multistep origin of tumours, it is important to examine the HLA expression in premalignant precursor lesions of tumours and in tumours themselves. Our studies have recently reported a downregulation of HLA class I expression in colorectal cancers and adenomatous polyps when compared to normal appearing mucosa adjacent to the cancer. Our study on the class I antigen expression showed the presence of the antigen on all samples of control colonic epithelium. In sporadic adenomatous polyps of the colorectum, 21% (n = 7) of adenomas expressed levels of HLA that were comparable to controls, 51% (n = 17) expressed low levels, and in 28% (n = 9) the antigen was undetectable. Similarly, in colorectal adenocarcinomas the antigen was reduced even further with levels comparable to controls in 5% (n = 2) of tumours, reduced in 30% (n = 6) and undetectable in 65% (n = 13). This abnormality may result in the loss of immunosurveillance which could be one mechanism by which cancer cells can evade "T" cell control, thus resulting in invasion and metastasis.