Loss of HLA class I expression in prostate cancer: implications for immunotherapy

There is currently no reliable predictor of the metastatic potential of apparently localized prostate cancer in an individual patient or satisfactory treatment for patients with advanced disease. One of the factors that may influence tumor progression is the cellular arm of the immune response, and central to this is the human leukocyte antigen (HLA) system, which acts to restrict T-cell recognition of potential tumor antigens. It has been reported in some cancers that down regulation of HLA class I expression by the tumor cells is associated with poor prognosis. In this report, HLA class I and II expression have been investigated in both benign and malignant prostate disease, first to define the extent of altered HLA expression and second to assess whether HLA expression may be related to disease progression.

HLA expression was assessed by immunohistochemistry utilizing a set of monoclonal antibodies that recognize both monomorphic determinants and the commoner HLA class I allelic products.

In contrast to the normal HLA class I expression of the benign tissue, complete loss of HLA class I expression occurred in 34% of primary prostate cancers and 80% of lymph node metastases. When individual allelic expression was assessed, the minimum estimate of down regulation was 85% in the primary prostate cancers and 100% of the metastases.

This investigation has demonstrated a higher rate of HLA class I loss than has been reported in other tumors and would suggest that the immune system may have an important role in the progression of prostate cancer, as well as having implications for the design and success of immunotherapy regimens in advanced disease.