title: [Cancer immunotherapy: Rational and recent breakthroughs].
abstract: Cancer immunotherapy has occupied a marginal therapeutic option in cancer despite strong arguments documenting the role of the immune system in controlling the proliferation of cancers. The recent success of immunotherapy results from a change in the past paradigm. From now on, the goal is not only to activate the immune system against tumor, but also to take account of the immunosuppressive tumor microenvironment Among these mechanisms, negative costimulatory molecules (CTLA-4, PD-1, etc.) expressed by T cells in the tumor could explain their lack of effectiveness in inhibiting tumor growth. Blocking these molecules allowed the reactivation of anti-tumor T cells. Clinically, the administration of anti-CTLA-4 antibody (ipilimumab: Yervoy®) was granted marketing authorization for patients with metastatic melanoma. The anti-PD-1 antibodies (nivolumab: Opdivo®, pembrolizumab: Keytruda®) have demonstrated clinical efficacy when compared to the standard therapy in metastatic melanomas, advanced lung cancers and metastatic renal cell carcinoma. In phase I and II clinical trials, other tumors (Hodgkin's disease, head and neck cancers, bladder cancer, gastric cancer, etc.) appear to be responsive to these immunomodulators. These treatments were associated with the occurrence of side effects dominated by autoimmunity predictable by unlocking the breaks exerted by immune system to maintain tolerance against self-antigen. The optimization of therapeutic combination based on these molecules and the search for biomarkers associated with these treatments constitute a challenge for the future for this new therapeutic class of drugs for oncology.
authors.affiliation: Inserm U970, Paris Cardiovascular Research Center - PARCC, 56, rue Leblanc, 75015 Paris, France; UMR-S970, université Paris-Descartes, Sorbonne-Paris-Cité, Paris, France; Équipe labellisée ligue contre le cancer, 56, rue Leblanc, 75015 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Granier
authors.affiliation: Inserm U970, Paris Cardiovascular Research Center - PARCC, 56, rue Leblanc, 75015 Paris, France; UMR-S970, université Paris-Descartes, Sorbonne-Paris-Cité, Paris, France; Équipe labellisée ligue contre le cancer, 56, rue Leblanc, 75015 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Karaki
authors.affiliation: Inserm U970, Paris Cardiovascular Research Center - PARCC, 56, rue Leblanc, 75015 Paris, France; UMR-S970, université Paris-Descartes, Sorbonne-Paris-Cité, Paris, France; Équipe labellisée ligue contre le cancer, 56, rue Leblanc, 75015 Paris, France; Service d'anatomie-pathologique, Assistance publique-Hôpitaux de Paris, hôpital européen Georges-Pompidou, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Roussel
authors.affiliation: Inserm U970, Paris Cardiovascular Research Center - PARCC, 56, rue Leblanc, 75015 Paris, France; UMR-S970, université Paris-Descartes, Sorbonne-Paris-Cité, Paris, France; Équipe labellisée ligue contre le cancer, 56, rue Leblanc, 75015 Paris, France; Service d'anatomie-pathologique, Assistance publique-Hôpitaux de Paris, hôpital européen Georges-Pompidou, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Badoual
authors.affiliation: Inserm U970, Paris Cardiovascular Research Center - PARCC, 56, rue Leblanc, 75015 Paris, France; UMR-S970, université Paris-Descartes, Sorbonne-Paris-Cité, Paris, France; Équipe labellisée ligue contre le cancer, 56, rue Leblanc, 75015 Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Tran
authors.affiliation: Inserm U970, Paris Cardiovascular Research Center - PARCC, 56, rue Leblanc, 75015 Paris, France; UMR-S970, université Paris-Descartes, Sorbonne-Paris-Cité, Paris, France; Équipe labellisée ligue contre le cancer, 56, rue Leblanc, 75015 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Anson
authors.affiliation: Service d'oncologie médicale, Assistance publique-Hôpitaux de Paris, hôpital européen Georges-Pompidou, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Fabre
authors.affiliation: Inserm U970, Paris Cardiovascular Research Center - PARCC, 56, rue Leblanc, 75015 Paris, France; UMR-S970, université Paris-Descartes, Sorbonne-Paris-Cité, Paris, France; Équipe labellisée ligue contre le cancer, 56, rue Leblanc, 75015 Paris, France; Service d'oncologie médicale, Assistance publique-Hôpitaux de Paris, hôpital européen Georges-Pompidou, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Oudard
authors.affiliation: Inserm U970, Paris Cardiovascular Research Center - PARCC, 56, rue Leblanc, 75015 Paris, France; UMR-S970, université Paris-Descartes, Sorbonne-Paris-Cité, Paris, France; Équipe labellisée ligue contre le cancer, 56, rue Leblanc, 75015 Paris, France; Service d'immunologie biologique, Assistance publique-Hôpitaux de Paris, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France. Electronic address: eric.tartour@aphp.fr.
authors.forename: E
authors.initials: E
authors.lastname: Tartour
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007167:Immunotherapy / Q000266:history / Q000379:methods / Q000592:standards / Q000639:trends*; D058990:Molecular Targeted Therapy / Q000379:methods / Q000592:standards / Q000639:trends; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines
keywords: Autoimmunity; Autoimmunité; Cancer; Immunosuppression; Immunotherapy; Immunothérapie; Microenvironnement des tumeurs; Tumor microenvironment