Specific activation of the non-classical class I histocompatibility HLA-G antigen and expression of the ILT2 inhibitory receptor in human breast cancer.

Abstract

The HLA-G molecule is a non-classical HLA class I antigen selectively expressed by trophoblastic cells that invade the maternal decidua during human pregnancy. HLA-G is believed to contribute to tolerance of the semi-allogeneic fetus by inhibiting maternal immune responses. Similarly, HLA-G expression in tumour cells may favour their escape from host immune surveillance. This study investigated HLA-G expression in human mammary tumours. Immunohistochemical analysis of cryo-preserved and paraffin-embedded breast tissue biopsies, using two HLA-G-specific antibodies, revealed that unlike non-cancerous breast tissue in the vicinity of the tumour, 14 out of 36 breast cancer lesions selectively expressed HLA-G. HLA-G expression was significantly more frequent in lesions that were highly infiltrated by host immune cells, thus correlating HLA-G activation with inflammation. Further histological and double-staining immunofluorescence analysis attributed HLA-G expression mainly to tumour epithelial cells and to subsets of infiltrating CD68+ and CD8+ cells. RT-PCR analysis suggested that HLA-G was activated at the transcriptional level in breast tumours. The presence of ILT2 (Ig-like transcript 2) killing inhibitory receptors known to interact with HLA-G was also demonstrated in host immune cells that infiltrate breast cancer lesions. These results indicate that HLA-G is up-regulated at high frequencies in human breast cancer, where it may impair efficient anti-tumour immunity.