Fig. 6: Defining PDAC subtype and organoid phenotype-specific vulnerabilities to radio- and chemotherapy.
a, Schematic representation of the in vitro workflow for the different treatment approaches with either FOLFIRINOX (FFX) IC50 values or 8 Gy irradiation; image created with BioRender.com. b,c, Average O-SFU per gel for epithelial (b) and mesenchymal (c) type of organoids. All organoid numbers correspond to 3 E-lines (IDs: 8442, 9591, 53631) and 3 M-lines (IDs: 8028, 9091, 16992). For all E and M-lines control n = 9, FFX n = 7, FFX W.O. n = 7, 8 Gy n = 4 and 8 Gy W.O. n = 4 individual experiments (except for the M-line ID: 8028 where control n = 7 individual experiments). Graphs represent median with interquartile range. Unpaired two-tailed non-parametric t-test, Mann–Whitney test. d, Representative organoid morphologies of epithelial (from 3 mouse lines) and mesenchymal (from 3 mouse lines) organoids before (control n = 2,438 organoids), after treatment with FFX (n = 1,470 organoids), 8 Gy irradiation (n = 428 organoids) or their washout phases (FFX W.O. n = 1,594 and 8 Gy W.O. n = 638 organoids). Scale bars, 500 µm. e, MRI images of the in vivo tumours at Day 14 after transplantation for epithelial (top) and mesenchymal (bottom) transplanted lines. Scale bars, 1 cm. f, Quantification of the tumour volume from the MRI measurements. Graph represents mean ± s.e.m, unpaired two-tailed parametric t-test with Welch’s correction, two-tailed. g, Representative H&E images of the transplanted tumours. Scale bars, 200 µm. h, Histological grading of the transplanted tumours (n = 33 mice); graph represents mean ± s.e.m. i, Manual phenotypic analysis of epithelial (n = 915 organoids, from the mouse line ID: 9591 from at least 3 individual experiments) and mesenchymal (n = 1,257 organoids, from the mouse line ID: 16992 from at least 3 individual experiments) organoids before, after treatment and in the respective washout phase. Pie charts represent the average number of organoid phenotypes (%).
