Molecular Pathways: Human leukocyte antigen G (HLA-G).

Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class I molecule that exerts important tolerogenic functions. Its main physiological expression occurs in placenta where participates in the maternal tolerance toward the fetus. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic lineage. It is expressed in various types of primary solid (melanoma, head and neck, lung, urogenital, gastrointestinal and breast cancers) and hematological malignancies (acute leukemia, lymphomas) and metastases. HLA-G ectopic expression is observed in cancer suggesting that its expression is one strategy used by tumor cells to escape immune surveillance. In this review, we will focus on HLA-G expression in cancers and its association with the prognosis. We will highlight the underlying molecular mechanisms of impaired HLA-G expression, the immune tolerant function of HLA-G in tumors, and the potential diagnostic use of membrane-bound and soluble HLA-G as a biomarker to identify tumors and to monitor disease stage. Since HLA-G is a potent immuno-inhibitory molecule, its blockade remains an attractive therapeutic strategy against cancer. Elimination of HLA-G-expressing cancer cells would be important in the efficacy of anti-cancer therapies.JOURNAL ARTICLE