Patient-derived tumoroids and proteomic signatures: tools for early drug discovery.

Fiche publication


Date publication

avril 2024

Journal

Frontiers in immunology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BENKIRANE-JESSEL Nadia, Dr LINDNER Véronique


Tous les auteurs :
Lê H, Deforges J, Cutolo P, Lamarque A, Hua G, Lindner V, Jain S, Balloul JM, Benkirane-Jessel N, Quéméneur E

Résumé

Onco-virotherapy is an emergent treatment for cancer based on viral vectors. The therapeutic activity is based on two different mechanisms including tumor-specific oncolysis and immunostimulatory properties. In this study, we evaluated onco-virotherapy responses on immunocompetent non-small cell lung cancer (NSCLC) patient-derived tumoroids (PDTs) and healthy organoids. PDTs are accurate tools to predict patient's clinical responses at the stage. We showed that onco-virotherapy could exert specific antitumoral effects by producing a higher number of viral particles in PDTs than in healthy organoids. In the present work, we used multiplex protein screening, based on proximity extension assay to highlight different response profiles. Our results pointed to the increase of proteins implied in T cell activation, such as IFN-γ following onco-virotherapy treatment. Based on our observation, oncolytic viruses-based therapy responders are dependent on several factors: a high PD-L1 expression, which is a biomarker of greater immune response under immunotherapies, and the number of viral particles present in tumor tissue, which is dependent to the metabolic state of tumoral cells. Herein, we highlight the use of PDTs as an alternative model to assess patient-specific responses to onco-virotherapy at the early stage of the preclinical phases.

Mots clés

Anti-cancer Therapy, immuno-oncology, non-small-cell lung cancer, onco-virotherapy, patient-derived tumoroids, proteomic

Référence

Front Immunol. 2024 04 18;15:1379613