Functional precision oncology for follicular lymphoma with patient-derived xenograft in avian embryos
Résumé
Despite achieving high rates of complete remission with RCHOP immuno-chemotherapy, almost all patients with follicular lymphoma (FL) will experience multiple relapses after treatment. The lack of experimental model of FL limits our understanding of treatment response heterogeneity. Here we characterized a new model of FL patient-derived xenograft in avian embryos. Based on 20 biopsy samples, we observed that tumor volume reduction achieved with RCHOP treatment in ovo predicted progression free survival in multivariate analysis. To further explore the model, we used single-cell RNA sequencing to discover a signature of 21 genes upregulated after RCHOP exposure, with significant intratumoral heterogeneity. Among these genes, we functionally validated BAX as a critical effector of RCHOP which can be targeted with venetoclax in vitro and in ovo. Overall, the FL-AVI-PDX model is a platform for functional precision oncology in FL, which captures both interpatient and intrapatient heterogeneity, and opens an avenue for drug development
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