Fig. 6: IFN-I signaling in PDOs primes TEG efficacy.
From: Uncovering the mode of action of engineered T cells in patient cancer organoids
a, Top: UMAP embedding of pooled scRNA-seq profiles from super engaged and nonengagedEnriched TEG populations cocultured with either 13T or 10T PDOs, and from no-target control T cells. TEGs are colored according to experimental condition. Bottom: UMAP plot showing expression levels of IFNG and GZMB. Colors represent log2-transformed normalized counts of genes. b, Venn diagrams depicting common and unique genes upregulated (up) in TEGs following 13T and 10T organoid exposure (top, environmental stimuli) or prolonged engagement (bottom, super engagers). c, Heatmap of gene expression for genes involved in functional annotations of interest in response to IFN-I, cytokine response), grouped according to TEG populations. d, IFNA and IFNB expression in PDOs from the BC panel in Fig. 1d. 1 and 2 indicate different experimental replicates. e–g, Quantification of dying single organoids in the presence or absence of recombinant IFN-β for the following conditions: organoids cocultured with TEGs with direct addition of IFN-β, corrected for responses of LM1 control T cells (e); organoids preincubated with IFN-β for 24 h before coculture with TEGs, corrected for responses of LM1 control T cells (f); and organoids preincubated with IFN-β for 24 h and cultured in the absence of TEGs (g). Lines connect experimental replicates. f, Statistical analysis was performed by paired t-test: 34T IFN-β versus 34T control, P < 0.0006 (***); 27T IFN-β versus 27T control, P < 0.0216 (*); 10T IFN-β versus 10T control, P < 0.0402 (*). See Supplementary Table 8 for summary of replicates in e–g.
