Fig. 4: Immunomodulatory effects of mutant KRAS in human PDAC.
From: KRAS drives immune evasion in a genetic model of pancreatic cancer
a Human PDAC samples (n = 178) derived from the TCGA database were divided into two groups according to a gene expression signature (KRAS-dependency index, RDI) that distinguishes putative KRAS-dependent (RDI > 4) and -independent cell states (RDI < 0) (top). Landscape of genomic alterations in the human PDAC tumors is shown (bottom). b, c Heatmaps derived from data in (a) depicting differentially expressed genes in KRAS-dependent tumors (n = 69) versus distinctive KRAS-independent tumors (n = 65). d Box plots showing TIL fraction in KRAS-dependent (n = 60) versus KRAS-independent tumors (n = 50), and KRAS-high (n = 60) versus KRAS-low tumors (n = 50) in the digital-pathology PDAC database40. Box plots show center line as median, box limits as upper and lower quartiles, and whiskers represent a 1.5× interquartile range. Significance was determined using two-tailed t-test at the 0.05 confidence interval. e Distribution of immune subtypes within KRAS-dependent (n = 60) and KRAS-independent tumors (n = 50): C1 (wound healing), C2 (IFNG dominant), C3 (inflammatory), and C6 (TGF-beta dominant). The proportion of samples belonging to each immune subtype is shown. Significance was determined using two-sided Fisher’s exact test. f Box plots showing leukocyte fraction in KRAS-dependent (n = 68) versus KRAS-independent tumors (n = 52), and KRAS-high (n = 68) versus KRAS-low tumors (n = 52) in the immune PDAC database34. Box plots show center line as median, box limits as upper and lower quartiles, and whiskers represent a 1.5× interquartile range. Significance was determined using two-tailed t-test at the 0.05 confidence interval. g Differential expression of immune checkpoint genes in KRAS-dependent (n = 68) and KRAS-independent tumors (n = 52). Significance was determined using two-tailed t-test at the 0.05 confidence interval. Tumors from b, c for which the immune information is available are considered in panels (d–g). Source data are available as a Source data file.
