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Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis.

• アブストラクト	Immune checkpoint inhibitors (ICI) have transformed the therapeutic landscape in oncology. However, ICI can induce uncommon life-threatening autoimmune T-cell-mediated myotoxicities, including myocarditis and myositis. The thymus plays a critical role in T cell maturation. Here we demonstrate that thymic alterations are associated with increased incidence and severity of ICI myotoxicities. First, using the international pharmacovigilance database VigiBase, the Assistance Publique Hopitaux de Paris-Sorbonne University data warehouse (Paris, France) and a meta-analysis of clinical trials, we show that ICI treatment of thymic epithelial tumors (TET, and particularly thymoma) was more frequently associated with ICI myotoxicities than other ICI-treated cancers. Second, in an international ICI myocarditis registry, we established that myocarditis occurred earlier after ICI initiation in patients with TET (including active or prior history of TET) compared to other cancers and was more severe in terms of life-threatening arrythmias and concurrent myositis, leading to respiratory muscle failure and death. Lastly, we show that presence of anti-acetylcholine-receptor antibodies (a biological proxy of thymic-associated autoimmunity) was more prevalent in patients with ICI myocarditis than in ICI-treated control patients. Altogether, our results highlight that thymic alterations are associated with incidence and seriousness of ICI myotoxicities. Clinico-radio-biological workup evaluating the thymus may help in predicting ICI myotoxicities.
  ジャーナル名	Nature medicine
  投稿日	2023/10/27
  投稿者	Fenioux, Charlotte; Abbar, Baptiste; Boussouar, Samia; Bretagne, Marie; Power, John R; Moslehi, Javid J; Gougis, Paul; Amelin, Damien; Dechartres, Agnes; Lehmann, Lorenz H; Courand, Pierre-Yves; Cautela, Jennifer; Alexandre, Joachim; Procureur, Adrien; Rozes, Antoine; Leonard-Louis, Sarah; Qin, Juan; Cheynier, Remi; Charmeteau-De Muylder, Benedicte; Redheuil, Alban; Tubach, Florence; Cadranel, Jacques; Milon, Audrey; Ederhy, Stephane; Similowski, Thomas; Johnson, Douglas B; Pizzo, Ian; Catalan, Toniemarie; Benveniste, Olivier; Hayek, Salim S; Allenbach, Yves; Rosenzwajg, Michelle; Dolladille, Charles; Salem, Joe-Elie
  組織名	Sorbonne Universite, INSERM, CIC-1901 Paris-Est, Assistance Publique - Hopitaux;de Paris, Pitie-Salpetriere Hospital, Department of Pharmacology, Paris, France.;Hopitaux de Paris, Henri Mondor Hospital, Department of Oncology, Creteil,;France.;Hopitaux de Paris, Pitie Salpetriere Hospital, Department of Oncology, Paris,;Hopitaux de Paris, Pitie Salpetriere Hospital, Department of Radiology, Paris,;Department of Medecine, University of California, San Diego, San Diego, CA, USA.;Department of Medecine, University of California, San Francisco, San Francisco,;CA, USA.;Sorbonne Universite, INSERM, Association Institut de Myologie, Center of Research;in Myology, UMRS 974, Paris, France.;Sorbonne Universite, INSERM, Institut Pierre Louis d'Epidemiologie et de Sante;Publique, Departement de Sante Publique, Centre de Pharmacoepidemiologie;(Cephepi), Unite de Recherche Clinique PSL-CFX, CIC-1901, AP-HP, Hopital Pitie;Salpetriere, Paris, France.;Department of Cardiology, University Hospital Heidelberg; German Cancer Research;Center (DKFZ), Heidelberg, Germany.;Federation de Cardiologie, IMMUCARE, Hopital de La Croix-Rousse Et Hopital Lyon;Sud, Hospices Civils de Lyon; Universite de Lyon, CREATIS UMR INSERM U1044, INSA,;Lyon, France.;Aix-Marseille University, University Mediterranean Center of Cardio-Oncology,;Unit of Heart Failure and Valvular Heart Diseases, Center for Cardiovascular and;Nutrition Research, INSERM 1263, INRAE 1260, Nord Hospital, Assistance;Publique-Hopitaux de Marseille, Paris, France.;CHU de Caen Normandie, Department of Pharmacology, Pharmacoepidemiology Unit;;Normandie Universite, UNICAEN, INSERM U1086 ANTICIPE Centre Francois Baclesse,;Caen, France.;Hopitaux de Paris, Pitie Salpetriere Hospital, Laboratoire de Neuropathologie,;Paris, France.;Universite Paris Cite, CNRS, INSERM, Institut Cochin, Paris, France.;Hopitaux de Paris, Tenon Hospital, Department of Pulmonology and Thoracic;Oncology and GRC Theranoscan Sorbonne University, Paris, France.;Hopitaux de Paris, Tenon Hospital, Department of Radiology, Paris, France.;Hopitaux de Paris, Saint-Antoine Hospital, Department of Cardiology, Paris,;Sorbonne Universite, INSERM, UMRS 1158 Neurophysiologie respiratoire;experimentale et clinique'; Assistance Publique -Hopitaux de Paris,;Pitie-Salpetriere Hospital, 'Departement R3S', Paris, France.;Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.;Department of Internal Medicine, Division of Cardiology, University of Michigan,;Ann Arbor, MI, USA.;Department of Internal Medicine, Sorbonne University, AP-HP, INSERM UMRS 974,;Pitie-Salpetriere Hospital, Paris, France.;Hopitaux de Paris, Pitie Salpetriere Hospital, Department of Immunology, Paris,;joe-elie.salem@aphp.fr.
  Pubmed リンク	https://www.ncbi.nlm.nih.gov/pubmed/37884625/

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