Role of altered expression of HLA class I molecules in cancer progression.
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.
Aptsiauri
Natalia
N
Departmiento de Analisis Clinicos, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Cabrera
Teresa
T
Mendez
Rosa
R
Garcia-Lora
Angel
A
Ruiz-Cabello
Francisco
F
Garrido
Federico
F
D019496:Cancer Vaccines; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods*; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D013601:T-Lymphocytes / Q000378:metabolism; D016896:Treatment Outcome
D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I