title: HLA-G: An Immune Checkpoint Molecule.
abstract: HLA-G is a molecule that was first known to confer protection to the fetus from destruction by the immune system of its mother, thus critically contributing to fetal-maternal tolerance. The first functional finding constituted the basis for HLA-G research and can be summarized as such: HLA-G, membrane-bound or soluble, strongly binds its inhibitory receptors on immune cells (NK, T, B, monocytes/dendritic cells), inhibits the functions of these effectors, and so induces immune inhibition. HLA-G function may therefore be beneficial because when expressed by a fetus or a transplant it protects them from rejection, or deleterious because when expressed by a tumor, it also protects it from antitumor immunity. This is the primary HLA-G function: that of a checkpoint molecule. Great work has been done in the past years to characterize HLA-G itself, its regulation, its functions and mechanisms of action, and its pathological relevance. We will review this here, focusing on transplantation and oncology because these pathological contexts have been studied the most and also because they best represent the two opposite sides of HLA-G: beneficial to be promoted, or deleterious to be blocked.
authors.affiliation: CEA, Institute of Emerging Diseases and Innovative Therapies (iMETI), Research Division in Hematology and Immunology (SRHI), Saint-Louis Hospital, Paris, France; University Paris Diderot, Sorbonne Paris Cité, UMR E_5 Institut Universitaire d'Hematologie, Saint-Louis Hospital, Paris, France.
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
authors.affiliation: CEA, Institute of Emerging Diseases and Innovative Therapies (iMETI), Research Division in Hematology and Immunology (SRHI), Saint-Louis Hospital, Paris, France; University Paris Diderot, Sorbonne Paris Cité, UMR E_5 Institut Universitaire d'Hematologie, Saint-Louis Hospital, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rouas-Freiss
authors.affiliation: CEA, Institute of Emerging Diseases and Innovative Therapies (iMETI), Research Division in Hematology and Immunology (SRHI), Saint-Louis Hospital, Paris, France; University Paris Diderot, Sorbonne Paris Cité, UMR E_5 Institut Universitaire d'Hematologie, Saint-Louis Hospital, Paris, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Tronik-Le Roux
authors.affiliation: CEA, Institute of Emerging Diseases and Innovative Therapies (iMETI), Research Division in Hematology and Immunology (SRHI), Saint-Louis Hospital, Paris, France; University Paris Diderot, Sorbonne Paris Cité, UMR E_5 Institut Universitaire d'Hematologie, Saint-Louis Hospital, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: CEA, Institute of Emerging Diseases and Innovative Therapies (iMETI), Research Division in Hematology and Immunology (SRHI), Saint-Louis Hospital, Paris, France; University Paris Diderot, Sorbonne Paris Cité, UMR E_5 Institut Universitaire d'Hematologie, Saint-Louis Hospital, Paris, France. Electronic address: joel.lemaoult@cea.fr.
authors.forename: Joel
authors.initials: J
authors.lastname: LeMaoult
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D059951:HLA-G Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic
chemical_list: D059951:HLA-G Antigens; D035683:MicroRNAs
keywords: Cancer; Checkpoint; Gene regulation; HLA-G; Immune escape; Immune regulation; Inhibitory receptors; Regulatory cells; Tolerance; Transplantation