Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
06
02
2023
accepted:
15
09
2023
pubmed:
27
10
2023
medline:
27
10
2023
entrez:
26
10
2023
Statut:
ppublish
Résumé
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 Hôpitaux 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.
Identifiants
pubmed: 37884625
doi: 10.1038/s41591-023-02591-2
pii: 10.1038/s41591-023-02591-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3100-3110Subventions
Organisme : Direction Générale de l'offre de Soins (DGOS)
ID : CIC-1901
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : R01HL141466
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : R01HL155990
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : R01HL156021
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : R01HL160688
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : R01HL153384
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : R01-DK128012
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : LE3570/2-1; 3570/3-1
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 01KC2006B
Investigateurs
Nausheen Akhter
(N)
Nazanin Aghel
(N)
Kingsley Amidi
(K)
Elizabeth Anderson
(E)
Dimitri Arangalage
(D)
Mandar Aras
(M)
Aarti Asnani
(A)
Lauren A Baldassarre
(LA)
Rocio Barovila
(R)
Ana Sofia Barroso
(AS)
Wendy Bottinor
(W)
Anissa Bouali
(A)
Eve Cariou
(E)
Wei-Ting Chang
(WT)
Richard K Cheng
(RK)
Shanthini M Crusz
(SM)
Anita Deswal
(A)
Pierre-Yves Dietrich
(PY)
Grace Dy
(G)
Clemence Docq
(C)
Steven Ewer
(S)
Suran Fernando
(S)
Danette L Flint
(DL)
Roberta Florido
(R)
Satoshi Fukushima
(S)
Elena Galli
(E)
Elizabeth Gaughan
(E)
Manhal Habib
(M)
Andrew Haydon
(A)
Lucie Heinzerling
(L)
Osnat Itzhaki Ben Zadok
(OI)
Nahema Issa
(N)
Anja Karlstaedt
(A)
Kazuo Kitagawa
(K)
Michael Layoun
(M)
Michal Laufer-Perl
(M)
Carrie Lenneman
(C)
Darryl Leong
(D)
Chloe Lesiuk
(C)
Joshua Levenson
(J)
Teresa López-Fernández
(T)
Yan Liu
(Y)
Kristen Machado
(K)
Pedro Moliner
(P)
Ryota Morimoto
(R)
Michel Obeid
(M)
Anna Narezkina
(A)
Nicolas Palaskas
(N)
Giovanni Peretto
(G)
Nicolas Piriou
(N)
Juan Carlos Plana
(JC)
Peter P Rainer
(PP)
Maxime Robert-Halabi
(M)
Fanny Rocher
(F)
Eugenia Rota
(E)
Francois Roubille
(F)
Theresa Ruf
(T)
Shahneen Sandhu
(S)
Francis Sanjeev
(F)
Nobuhiko Seki
(N)
Kazuko Tajiri
(K)
Yuichi Tamura
(Y)
Franck Thuny
(F)
Romain Tresorier
(R)
Isik Turker
(I)
Ellen Warner
(E)
Vlad Zaha
(V)
Han Zhu
(H)
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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