abstract: AUTOIMMUNITY AND MANAGEMENT OF THE IMMUNE-RELATED ADVERSE EFFECTS OF THE IMMUNE CHECKPOINT INHIBITORS: The immune checkpoint molecules such as CTLA-4 and PD-1 are involved in the tolerance mechanisms preventing the immune system to react against the self-antigens. When these receptors expressed on the lymphocyte membrane, bind to their ligands, they induce a negative signal to the cell which becomes unable to be completely activated in the presence of its antigen. In a context of tumor, the infiltrating T cells are frequently exhausted due to the expression of CTLA-4 and PD-1 ligands by the microenvironment impairing the antitumoral immunity. The use of antagonistic antibodies targeting these receptors or their ligands (called checkpoint inhibitors) aims to block their interaction unbalancing the negative regulation of the antitumoral lymphocytes. However, this effect affects all lymphocytes and may also disrupt the negative regulation of the peripheral autoreactive lymphocytes. Thus, a significant proportion of patients treated by these molecules develop immune-related symptoms affecting different tissues and organs due to lymphocyte activation. These symptoms are called immune-related adverse events (irAEs). This article aims to summarize the scientific data demonstrating the implication of these molecules in the tolerance mechanisms and in the autoimmune diseases. It also reports on the IrAEs observed in treated patients and gives an outline of guidelines to monitor and manage these patients.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service d'immunologie biologique, hôpital européen Georges-Pompidou, Assistance publique-hôpitaux de Paris. Electronic address: marie.senant@aphp.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Senant
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service d'immunologie biologique, hôpital européen Georges-Pompidou, Assistance publique-hôpitaux de Paris. Electronic address: delphine.giusti@aphp.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Giusti
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service d'immunologie clinique, hôpital européen Georges-Pompidou, Assistance publique-hôpitaux de Paris.
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service d'immunologie biologique, hôpital européen Georges-Pompidou, Assistance publique-hôpitaux de Paris.
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Dragon-Durey
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Auto-immunité; Checkpoint Inhibiteurs; Effets indésirables liés à une immunothérapie; Immune checkpoint inhibitors; Immune-related Adverse events; Immunotherapy; Immunothérapie; autoimmunity