Titre :

Inhibition of furin in CAR macrophages directs them toward a proinflammatory phenotype and enhances their antitumor activities.

Auteur(s) :

Ziane Chaouche, Lydia [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Raffo Romero, Antonella [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Hajjaji, Nawale [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Kobeissy, Firas [Auteur]
American University of Beirut [Beyrouth] [AUB]
Pinheiro, Donna [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Aboulouard (Admin), Soulaimane [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Cozzani, Adeline [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Mitra, Suman [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Fournier, Isabelle [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Cizkova, Dasa [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Salzet, Michel [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Duhamel, Marie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]

Titre de la revue :

Cell Death and Disease

Pagination :

879

Éditeur :

Nature Publishing Group

Date de publication :

2024-12-07

ISSN :

2041-4889

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Chimeric antigen receptor (CAR)-T-cell therapy has revolutionized cellular immunotherapy, demonstrating remarkable efficacy in hematological cancers. However, its application in solid tumors faces significant challenges, ...
Lire la suite >Chimeric antigen receptor (CAR)-T-cell therapy has revolutionized cellular immunotherapy, demonstrating remarkable efficacy in hematological cancers. However, its application in solid tumors faces significant challenges, including limited T-cell infiltration and tumor-induced immunosuppression. Given the prominent role of macrophages in the tumor microenvironment, their phenotypic plasticity and inherent antitumor properties, such as phagocytosis, offer a promising avenue for therapeutic intervention. This study focuses on the development of a second generation of CAR macrophages (CAR-Ms). We elucidated the role of the proprotein convertase furin in macrophages, demonstrating its overexpression in the presence of tumor cells. Importantly, furin inhibition maintains a proinflammatory macrophage phenotype, potentially redirecting them towards an antitumor state. Compared to furin-expressing counterparts, furin-inhibited CAR-Ms exhibited heightened antitumor phagocytic activity against breast cancer cells and ex vivo patient-derived tumoroids. Notably, they sustained a persistent proinflammatory profile, indicative of enhanced tumoricidal potential. Additionally, furin-inhibited CAR-Ms secreted factors that promote T-cell activation, offering a means to modulate the tumor microenvironment. In summary, our work highlights the translational potential of furin-inhibited CAR-Ms as a potent cellular therapy to mitigate macrophage exhaustion within the tumor environment. By capitalizing on macrophage-mediated antitumor responses, these findings pave the way for the development of second-generation CAR-M therapeutic strategies tailored for solid tumors.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL

Date de dépôt :

2025-02-06T04:50:26Z