Radiation therapy and platinum-based chemotherapy are common treatments for lung cancer patients. Several factors are considered for the low overall survival rate of lung cancer, such as the patient’s physical state and the complex heterogeneity of the tumor, which leads to resistance to the treatment. Consequently, precision medicines are needed for the patients to improve their survival and their quality of life. Until now, no patient-derived tumoroid model has been reported to predict the efficiency of radiation therapy in non-small-cell lung cancer. Using our patient-derived tumoroid model, we report that this model could be used to evaluate the efficiency of radiation therapy and cisplatin-based chemotherapy in non-small-cell lung cancer. In addition, these results can be correlated to clinical outcomes of patients, indicating that this patient-derived tumoroid model can predict the response to radiotherapy and chemotherapy in non-small-cell lung cancer.

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.

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