HLA-G and its KIR ligands in cancer--another enigma yet to be solved?

Alterations of antigen-presenting human leukocyte antigen (HLA) molecules often occur in cancer and represent one of the mechanisms by which tumours evade host immunosurveillance. One such molecule, HLA-G, was recently implicated in the same context. HLA-G is thought to mediate the tolerance of the semi-allogeneic fetus during pregnancy, by inhibiting maternal immune response through interaction with different HLA-G-recognizing killer-cell inhibitory receptors (KIRs). A report in this issue of the journal demonstrates for the first time the expression of HLA-G and its KIR ligand, ILT-2 in human breast cancer. Apart from the up-regulation on tumour cells, the authors describe HLA-G induction on the macrophages and T cells infiltrating the breast cancer lesions. Moreover, a subset of infiltrating cells also expressed HLA-G-recognizing KIR, ILT-2. This editorial discusses the induction of HLA-G and related KIR molecules as another mechanism for tumours to escape immune recognition.