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. 2021 Feb 18;12:1117. doi: 10.1038/s41467-021-21300-6

Fig. 3. Correlation of genomic features and specific drug responses in organoid models.

Fig. 3

a–c Time course of ATP-mediated luminescence viability assay following a single dose of 10 Gy irradiation on organoids derived from PNPCa (a), LAPC9 (b), and BM18 (c) PDX tumors. Mean ± SD is reported, N = 4 technical replicates (t = 0), N = 5 (for each of the t = 24, 48, 72, 96 h time points). Ordinary two-way ANOVA with Tukey multiple comparison test was performed. ****p < 0.0001. d Graph representing the percentage of contribution of specific mutagenic processes based on mutational signatures from PNPCa T1 (primary tumor), PDX (passages P2-P4) and organoids (from P4 PDX). e MSI status based on MSIsensor algorithm (https://github.com/ding-lab/msisensor), score ≥ 3.5 indicates MSI-high. f PD-L1 IHC staining on positive control (placenta tissue), primary T1 tumor, PNmet needle biopsy, PDX1 and PDX2 of the PNmet, and cytosmear of PDX-organoids. Images of representative areas per tumor sample are shown, relative to the positive control staining. g. Gene expression levels of immune markers based on RT-qPCR results on PNPCa organoids RNA at baseline (black bars) and after 48 h exposure to IFN-γ (red bars). Mean ± SD is reported, for VSIR N = 3, for PD-L1 N = 6, for PD-1, HLA-A, HLA-B N = 5 technical replicates, across two independent experiments. Two-tailed nested t-test. ****p < 0.0001. h–j MLR assay showing lymphocyte reactivity, Treg fraction and expression levels of surface PD-1, following coculture of PDX-derived PNPCa organoids with T cells and allogeneic, monocyte-derived dendritic cells (DCs). Mean ± SD is reported, h N ≥ 3 biologically independent samples per condition, N = 2 mDC+ IFN-γ from four independent experiments; Mixed effects analysis (REML) with Geisser–Greenhouse’s correction and Dunnett’s post-hoc test was performed. i N = 3 biologically independent experiments; one-way ANOVA with Dunnett’s correction for multiple comparisons was performed, j N = 2 per condition from two biologically independent experiments. IHC, immunohistochemistry; MLR, mixed lymphocyte reaction.