The role of classical and non-classical HLA class I antigens in human tumors

Semin Cancer Biol. 2012 Aug;22(4):350-8. doi: 10.1016/j.semcancer.2012.03.003. Epub 2012 Mar 24.


In human tumors alterations in the surface expression and/or function of the major histocompatibility complex (MHC) class I antigens are frequently found and equip neoplastic cells with mechanisms to escape immune control. The aberrant expression of HLA class I molecules can be caused by structural alterations or dysregulations of genes encoding the classical HLA class I antigens and/or components of the HLA class I antigen processing machinery (APM). The dysregulation of APM components could occur at the epigenetic, transcriptional or post-transcriptional level. In some malignancies these abnormalities are significantly associated with a higher tumor staging, grading, disease progression and a reduced survival of patients as well as a failure to CD8(+) T cell-based immunotherapies. In addition to HLA class I abnormalities, expression of the non-classical HLA-G antigen is often induced in tumors, which could be mediated by various microenvironmental factors. Interestingly, soluble HLA-G serum and plasma levels have been useful markers for the prediction of some malignancies. The biological consequence of HLA-G expression or sHLA-G is an escape from T and NK cell-mediated recognition. Thus, alterations of non-classical and classical HLA class I antigens and components of the antigen processing pathway provide tumor cells with different mechanisms to inactivate immune responses resulting in tumor growth and evasion from host immune surveillance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigen Presentation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / immunology
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class I / physiology*
  • Humans
  • Interferon-gamma / metabolism
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Signal Transduction
  • Tumor Escape


  • Histocompatibility Antigens Class I
  • Interferon-gamma