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Role of Altered Expression of HLA Class I Molecules in Cancer Progression

  • Natalia Aptsiauri
  • Teresa Cabrera
  • Rosa Mendez
  • Angel Garcia-Lor
  • Francisco Ruiz-Cabello
  • Federico Garrido
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 601)

Abstract

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.

Keywords

Melanoma Cell Line Tumor Escape Immune Selection Haplotype Loss Tumor Cell Elimination 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Natalia Aptsiauri
    • 1
  • Teresa Cabrera
    • 1
  • Rosa Mendez
    • 1
  • Angel Garcia-Lor
    • 1
  • Francisco Ruiz-Cabello
    • 1
  • Federico Garrido
    • 1
  1. 1.Departmiento de Analisis ClinicosHospital Universitario Virgen de las NievesGranadaSpain

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