Fig. 4. Enhanced tumor cell-intrinsic immune program induction is driven by optimized MAPK inhibition.

a, The log₂FC of gene expression (measured by qPCR) of indicated ISGs and the average of log₂FC of MAPK-regulated transcripts in patient-derived organoids treated with DT or DE for 72 h. Organoids are arranged based on the PFS data of patients (from left to right: longest to shortest PFS). b, GO term enrichment analysis of upregulated DEGs (log₂FC ≥ 1, P < 0.05, Fisher exact test) in organoids treated with 72-h DT or DE versus control. Gene expression was measured by bulk RNAseq. Organoids are arranged based on patient PFS data. c, Delta of ISG scores (left) and MAPK scores (right; 72-h treatment versus control) in DT-treated (n = 10) and DE-treated (n = 10) organoids (two-tailed Wilcoxon rank sum test). d, Delta of ISG scores (72-h treatment versus control) in organoids derived from patients with PFS > 6 months (n = 5) and PFS < 6 months (n = 5; two-tailed Wilcoxon rank sum test). In c and d, the box plots show the median, Q1 and Q3 (25th and 75th percentiles) of the data; the upper and lower whiskers extend to the minimum and maximum values. e, Pearson correlation (two sided) of ISG score delta and MAPK score delta in all DT- and DE-treated organoids.