Vascularized patient-derived tumoroids supplemented with immune cells to predict response towards treatment for lung cancer patients

Author:

Lê Hélène1,Ponté Charlotte2,Desforges Jules1,Hua Guoqiang2,Idoux-Gillet Ysia2,Lindner Véronique2,Olland Anne2,Falcoz Pierre-Emanuel2,Zaupa Cécile3,Quéméneur Eric1,Balloul Jean-Marc1,Jessel Nadia2

Affiliation:

1. Transgène SA

2. INSERM (French National Institute of Health and Medical Research)

3. Boehringer Ingelheim

Abstract

Abstract We here describe a prototype of a patient-derived tumoroid that prefigures the precision medicine approach by helping experimental assessment of response to current treatments. The introduction of microvessels to help forming a tumor-connected vasculature, and of peripheral blood immune cells was shown to be essential for the representativeness of the model. The study is based on a cohort of 11 patients at various stages of the disease. Noteworthy, this predictive vascularized, and immunocompetent micromodel can be obtained within 2 weeks, matching the constraints of the patient journey. Histological analyses confirmed that major features of the original tumor were conserved. Transcriptomic analysis confirmed the functionality of the tumoroid. The responses to either anti-angiogenic treatment or platinum-based chemotherapy regimen highlighted the role of immune mechanisms. We also discussed the possibility to apply this original experimental model to the analysis of response to immune checkpoint blockers, or oncolytic vector-based therapies.

Publisher

Research Square Platform LLC

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