In vitro vascularized immunocompetent patient-derived model to test cancer therapies.

Fiche publication

Date publication

octobre 2023

Journal

iScience

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BENKIRANE-JESSEL Nadia , Pr FALCOZ Pierre-Emmanuel , Dr LINDNER Véronique , Dr IDOUX-GILLET Ysia , Pr OLLAND Anne

Tous les auteurs :
Lê H, Deforges J, Hua G, Idoux-Gillet Y, Ponté C, Lindner V, Olland A, Falcoz PE, Zaupa C, Jain S, Quéméneur E, Benkirane-Jessel N, Balloul JM

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/37860774

Résumé

This work describes a patient-derived tumoroid model (PDTs) to support precision medicine in lung oncology. The use of human adipose tissue-derived microvasculature and patient-derived peripheral blood mononuclear cells (PBMCs) permits to achieve a physiologically relevant tumor microenvironment. This study involved ten patients at various stages of tumor progression. The vascularized, immune-infiltrated PDT model could be obtained within two weeks, matching the requirements of the therapeutic decision. Histological and transcriptomic analyses confirmed that the main features from the original tumor were reproduced. The 3D tumor model could be used to determine the dynamics of response to antiangiogenic therapy and platinum-based chemotherapy. Antiangiogenic therapy showed a significant decrease in vascular endothelial growth factor (VEGF)-A expression, reflecting its therapeutic effect in the model. In an immune-infiltrated PDT model, chemotherapy showed the ability to decrease the levels of lymphocyte activation gene-3 protein (LAG-3), B and T lymphocyte attenuator (BTLA), and inhibitory receptors of T cells functions.