DANTZER, Camille; VACHÉ, Justine; BRUNEL, Aude; MAHOUCHE, Isabelle; RAYMOND, Anne-Aurélie; DUPUY, Jean-William; PETREL, Melina; BIOULAC-SAGE, Paulette; PERRAIS, David; DUGOT-SENANT, Nathalie; VERDIER, Mireille; BESSETTE, Barbara; BILLOTTET, Clotilde; MOREAU, Violaine

doi:10.7554/eLife.95191

Voir/Ouvrir

Dantzer et al. - 2024 - Emerging role of oncogenic ß-catenin in exosome bi.pdf (4.092Mo)

Métadonnées

Afficher la notice complète

Licence d’utilisation du document

DANTZER, Camille
BoRdeaux Institute in onCology [Inserm U1312 - BRIC]

VACHÉ, Justine
BoRdeaux Institute in onCology [Inserm U1312 - BRIC]

BRUNEL, Aude
Contrôle de l’Activation Cellulaire, Progression Tumorale et Résistance thérapeutique [CAPTuR]

Langue

Article de revue

Ce document a été publié dans

eLife. 2024, vol. 13, p. 95191

Résumé en anglais

Immune checkpoint inhibitors have produced encouraging results in cancer patients. However, the majority of ß-catenin-mutated tumors have been described as lacking immune infiltrates and resistant to immunotherapy. The mechanisms by which oncogenic ß-catenin affects immune surveillance remain unclear. Herein, we highlighted the involvement of ß-catenin in the regulation of the exosomal pathway and, by extension, in immune/cancer cell communication in hepatocellular carcinoma (HCC). We showed that mutated ß-catenin represses expression of SDC4 and RAB27A , two main actors in exosome biogenesis, in both liver cancer cell lines and HCC patient samples. Using nanoparticle tracking analysis and live-cell imaging, we further demonstrated that activated ß-catenin represses exosome release. Then, we demonstrated in 3D spheroid models that activation of β-catenin promotes a decrease in immune cell infiltration through a defect in exosome secretion. Taken together, our results provide the first evidence that oncogenic ß-catenin plays a key role in exosome biogenesis. Our study gives new insight into the impact of ß-catenin mutations on tumor microenvironment remodeling, which could lead to the development of new strategies to enhance immunotherapeutic response.Author's response and modifications : https://doi.org/10.7554/elife.95191.3.sa4< Réduire

Voir/Ouvrir

Métadonnées

Partager cette publication !

Licence d’utilisation du document

Emerging role of oncogenic ß-catenin in exosome biogenesis as a driver of immune escape in hepatocellular carcinoma

Langue

Ce document a été publié dans

Résumé en anglais

URI

DOI

Unités de recherche