Loss of nonclassical MHC molecules MIC-A/B expression during progression of uveal melanoma

Br J Cancer. 2004 Oct 18;91(8):1495-9. doi: 10.1038/sj.bjc.6602123.


Uveal melanoma differs from cutaneous melanoma with respect to aetiology, metastatic behaviour and immune biology. The notion that loss of classical MHC class I molecules in uveal melanoma lesions is associated with an improved prognosis suggests that NK cells act as the predominant cells responsible for immune surveillance of this tumour. Consequently, immune escape mechanisms of uveal melanoma should impair the innate immunity. To this end, expression of the ligand for the NK receptor NKG2D, that is, MIC-A/B was expressed by 50% of primary tumours, but none of the metastatic lesions. MIC+ tumours were characterised by a NKG2D+ infiltrate, which was absent in MIC- lesions subsequent to chemoimmune therapy. Strikingly, MIC-A/B expression in metastatic lesions was observed subsequent to chemotherapy with fotemustine in one case. In summary, MIC/NKG2D interactions seem to be involved in the immune surveillance of primary uveal melanomas, whereas for metastatic tumours this ligand/receptor system seems not to be relevant, thus, suggesting an immune selection of MIC negative tumour cells.

MeSH terms

  • CD57 Antigens / metabolism
  • Disease Progression
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunity, Cellular
  • Immunoenzyme Techniques
  • Ligands
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Membrane Proteins / metabolism
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / metabolism
  • Receptors, Natural Killer Cell
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Uveal Neoplasms / metabolism*
  • Uveal Neoplasms / pathology


  • CD57 Antigens
  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • Ligands
  • MHC class I-related chain A
  • MICB antigen
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell