Soluble HLA-G, its diagnostic and prognostic value and potential target molecule for future therapy in cancer

Human leukocyte antigen G (HLA-G) is a non-classical MHC class I molecule that regulates many immune functions. The physiologic HLA-G expression is restricted to foetal tissues such as: amniotic cells, erythroid precursors, and cytotrophoblasts, and, in adults, to immune-privileged organs. The ectopic expression in tumours could point out to a strategy used by malignant cells to escape the immune surveillance. There are two forms of HLA-G, membrane-bound and soluble. The structure of the soluble and membrane bound isoforms differs at the C-terminus. The extracellular domain and the intracytoplasmic tail are replaced in the secreted isoforms by a short hydrophilic tail. These differences could serve as a marker to distinguish shed or proteolytically cleaved HLA-G isoforms from secreted HLA-G isoforms. HLA-G induces tolerance by inhibiting different cells and this function is mediated by binding of both soluble and membrane-bound HLA-G to the inhibitory receptors. There exists a consistent evidence in literature that HLA-G represents an important factor in determining prognosis in various types of cancer. In this review, we will focus on soluble form of HLA-G (sHLA-G) in cancers and its association with the prognosis of cancer patients, because this immune check-point molecule appears as a promising relevant target for cancer immunotherapy (Fig. 2, Ref. 115). Keywords: cancer, diagnosis, HLA-G, soluble HLA-G, tumour.