title: Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
abstract: Embryos and tumors are both masses of dividing cells expressing foreign Ags, but they are not rejected by the immune system. We hypothesized that similar tolerogenic mechanisms prevent their rejection. Global comparison of fetal and tumor microenvironments through transcriptomics in mice revealed strikingly similar and dramatic decreases in expression of numerous immune-related pathways, including Ag presentation and T cell signaling. Unsupervised analyses highlighted the parallel kinetics and similarities of immune signature downregulation, from the very first days after tumor or embryo implantation. Besides upregulated signatures related to cell proliferation, the only significant signatures shared by the two conditions across all biological processes and all time points studied were downmodulated immune response signatures. Regulatory T cell depletion completely reverses this immune downmodulation to an immune upregulation that leads to fetal or tumor immune rejection. We propose that evolutionarily selected mechanisms that protect mammalian fetuses from immune attack are hijacked to license tumor development.
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Laboratoire I3 (Immunologie-Immunopathologie-Immunothérapie), F-75013 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75013 Paris, France; and.
authors.forename: Djamel
authors.identifier: http://orcid.org/0000-0001-6002-5021
authors.initials: D
authors.lastname: Nehar-Belaid
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Laboratoire I3 (Immunologie-Immunopathologie-Immunothérapie), F-75013 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75013 Paris, France; and.
authors.forename: Tristan
authors.initials: T
authors.lastname: Courau
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Laboratoire I3 (Immunologie-Immunopathologie-Immunothérapie), F-75013 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75013 Paris, France; and.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dérian
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Laboratoire I3 (Immunologie-Immunopathologie-Immunothérapie), F-75013 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75013 Paris, France; and.
authors.forename: Laura
authors.initials: L
authors.lastname: Florez
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Laboratoire I3 (Immunologie-Immunopathologie-Immunothérapie), F-75013 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75013 Paris, France; and.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ruocco
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Laboratoire I3 (Immunologie-Immunopathologie-Immunothérapie), F-75013 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75013 Paris, France; and Assistance-Publique Hopitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Département de Biothérapies et Centre d'Investigation Clinique en Biothérapie, F-75013 Paris, France david.klatzmann@upmc.fr.
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
mesh_terms: D000818:Animals; D005260:Female; D047109:Fetal Development / Q000276:immunology*; D005333:Fetus / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059467:Transcriptome; D019139:Tumor Escape / Q000276:immunology*