Beyond the increasing complexity of the immunomodulatory HLA-G molecule

Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells

“…These cells were tumor-derived since they carried MYCN amplification as homogeneously staining regions ( Figure 6B, 1 and 2). Most human TECs expressed hCD105, a marker of EC activation [53] (Figure 6B, 3), HLA-class I ( Figure 6B, 4) but not HLA-class II (data not shown) antigens, as well as HLA-G, a non-polymorphic HLA-class Ib molecule expressed by embryonic cytotrophoblast cells and endowed with potent immunosuppressive activities [54] ( Figure 6B, 5). At variance with TEC, bulk tumor cells did not express PSMA, vWF, CD105, HLA-class I or HLA-G ( Figure 6A).…”

HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction

“…In addition, inhibition is also provided by interactions of inhibitory KIR with HLA-C and by ILT2 with HLA-G. 13 What is the role of HLA-G, a non-classical MHC molecule that is unusual in that it is uniquely restricted to fetal extravillous trophoblast cells under normal physiological conditions? The dogma that HLA-G has a key role in tolerance at the maternal/fetal interface by protecting the fetus from attack by NK cells of the mother 14 is losing ground, as recent findings do not support such a role. [15][16][17][18] Earlier reports on the inhibitory effects of HLA-G used total peripheral blood mononuclear cells to study NK cell cytotoxic activity.…”

Identification of a novel HLA-G+ regulatory population in blood: expansion after allogeneic transplantation and de novo HLA-G expression at graft-versus-host disease sites

“…1,2 Specifically, HLA-G was found to be expressed at the fetal-maternal interface of human placenta where it inhibits maternal natural killer cells protecting the fetus from immune attack and rejection. 3 Contrary to classical HLA class I molecules, HLA-G is not ubiquitously expressed after prenatal life.…”

“…In healthy adults, HLA-G translation is epigenetically repressed and constitutive HLA-G expression was found only in immune-privileged tissues, such as thymus and cornea. 2 Besides this highly tissue-restricted expression, some authors have observed HLA-G cell surface expression in some peripheral blood (PB) monocytes from healthy individuals 4-7 while Feger et al 8 have recently found that thymus generates a discrete subset of naturally occurring HLA-G pos T cells with regulatory properties. Beyond physiological conditions, ectopic HLA-G expression has been found in tumor cells, 9 virus infected cells, 7 transplanted organs or immune cells infiltrating grafts, 3 and has been suggested to constitute an immune escape mechanism.…”

“…HLA-G exerts the above immunoregulatory functions by engaging inhibitory receptors (immunoglobulin-like transcript (ILT)-2, ILT-4 and the killer immunoglobulin-like(KIR)2DL4) on immune effector cells without any need for peptide presentation, resulting in a transient block in their functions. 2 Furthermore, it has been shown that HLA-G molecules can be intercellularly transferred from HLA-G + cells to activated T cells and NK cells by trogocytosis, making them from effector to immunoregulatory cells. 18,19 The immunosuppressive functions of HLA-G are strengthened by in vivo studies showing that injection of HLA-G tetramer-coated beads into mice 20 or use of HLA-G/human β2-microglobulin transgenic mice 21 promoted skin allograft survival and that HLA-G expression in tumor cells favored their evasion in xenotumor mouse models.…”