HLA
class I antigens play a key role in immune recognition of transformed and virally infected cells via binding to the
peptides of "non-self" or aberrantly expressed
proteins and subsequent presentation of the newly formed "HLA-I-
peptide" complex to T lymphocytes. Consequently, a chain of immune reactions is initiated leading to
tumor cell elimination by cytotoxic T cells. Altered
tumor expression of HLA class I is frequently observed in various types of
malignancies. It represents one of the main mechanisms used by
cancer cells to evade immunosurveillance. Because of immune selection, HLA class I-negative variants escape and lead to
tumor growth and metastatic colonization. Loss or downregulation of HLA
class I antigens on
tumor cell surface is
a factor that limits clinical outcome of
peptide-based
cancer vaccines aimed to increasing specific anti-
tumor activity of cytotoxic T lymphocytes. Thus, gaining more knowledge regarding frequency of HLA class I defect, its tissue specificity, and underlying molecular mechanisms may help designing appropriate therapeutic strategies in
cancer treatment. Here, we describe various types of HLA class I alterations found in different
malignancies and molecular mechanisms that underlie these defects. We also discuss a correlation between HLA class I defects
cancer progression in
melanoma patients with poor clinical response to autologous vaccination.