Impaired FADD/BID signaling mediates cross-resistance to immunotherapy in Multiple Myeloma.

Journal

Communications biology

ISSN: 2399-3642

Titre abrégé: Commun Biol

Pays: England

ID NLM: 101719179

Informations de publication

Date de publication:
21 Dec 2023

Historique:

received: 03 07 2023

accepted: 06 12 2023

medline: 22 12 2023

pubmed: 22 12 2023

entrez: 22 12 2023

Statut: epublish

Résumé

The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine treatment algorithms, resulting in improved response rates. Nevertheless, patients continue to relapse and the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has been reported to mediate resistance to CART in acute lymphoblastic leukemia, this mechanism yet remains to be elucidated in context of novel immunotherapies for MM. Here, we describe impaired death receptor signaling as a novel mechanism of resistance to T-cell mediated immunotherapies in MM. This resistance seems exclusive to novel immunotherapies while sensitivity to conventional anti-tumor therapies being preserved in vitro. As a proof of concept, we present a confirmatory clinical case indicating that the FADD/BID axis is required for meaningful responses to novel immunotherapies thus we report impaired death receptor signaling as a novel resistance mechanism to T-cell mediated immunotherapy in MM.

Identifiants

DOI: 10.1038/s42003-023-05683-4 PMID: 38129580

pubmed: 38129580

doi: 10.1038/s42003-023-05683-4

pii: 10.1038/s42003-023-05683-4

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

1299

Informations de copyright

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