04/11/2024 - Mirko MININI : Activated Gold-Nanoparticles enhance PD-1 blockade and boost cytotoxic T cell anti-tumor responses
16 - Octobre - 2024
LES LUNDIS DE SAINT-ANTOINE
Bâtiment Kourilsky - 11h–12h
Salle des Conférences (Rez de Chaussée),
184 rue du Faubourg Saint-Antoine, Paris
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LUNDI 04 NOVEMBRE 2024
Activated Gold-Nanoparticles enhance PD-1 blockade and boost cytotoxic T cell anti-tumor responses
Mirko MININI
Post-Doctorant, Centre de Recherche Saint Antoine (CRSA), Paris
équipe de Jérémie GAUTHERON (laura.fouassier@inserm.fr)
During the last decade, immunotherapy has revolutionized cancer treatment. However, the immune-resistant tumor microenvironment (TME) often compromises its efficacy in solid tumours. The dense extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) contribute to a rigid stroma in fibrotic tumors, like cholangiocarcinoma (CCA), hindering immune cell infiltration and fostering immunosuppression. Overcoming these physical and biological barriers is critical to fully unleash the potential of immunotherapeutic approaches. Here, we demonstrate that combining photothermal therapy (PTT) with gold iron oxide nanoparticles (GIONFs) effectively remodels the TME, reducing its stiffness and promoting a more permissive environment for immune cell infiltration. This mechanical alteration of the TME, combined with PD-1 blockade, enhances T-cell activation and reduces the immunosuppressive activity of CAFs. In preclinical models, this combination therapy significantly boosts immune responses and improves tumor control. These findings reveal the potential of reshaping the TME as a strategy to overcome immune resistance in fibrotic solid tumors like CCA by targeting both the ECM and immune checkpoints, thereby improving the efficacy of immunotherapy.
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