Altered expression of nonclassical HLA class Ib antigens in human renal cell carcinoma and its association with impaired immune response.

An optimal antitumoral immune response requires the activation of both CD8(+) and CD4(+) T lymphocytes by the peptide antigen presentation via the human leukocyte antigen (HLA) class I and class II molecules, respectively. Downregulation or loss of HLA molecules has been found in human renal cell carcinoma (RCC) and provides a strategy of these tumors to evade T-cell mediated immunosurveillance. In addition, a tumor-specific upregulation of HLA-G has been recently described in RCC, which also leads to an impaired immune response. We here summarize the frequency of the constitutive and/or interferon-gamma (IFN-gamma) inducible expression of nonclassical HLA class Ib antigens in RCC cell lines, surgically removed RCC lesions and normal kidney epithelium, the molecular characteristics of HLA-G expression, and its role in immune recognition.