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

• DOI: 10.7554/elife.95191.1
• Publication Date: 2024-03-19T01:32:01Z
• Authors: Camille Dantzer; Justine Vaché; Aude Brunel; Isabelle Mahouche; Anne-Aurélie Raymond; Jean-William Dupuy; Melina Petrel; Paulette Bioulac-...; David Perrais; Nathalie Dugot-Se...; Mireille Verdier; Barbara Bessette; Clotilde Billottet; Violaine Moreau
• Keywords: Exosome; Immune escape

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