Fig. 7: Wild-type Kras deficient KPN cells show reduced metastatic capacity and increased immune infiltration.

a Schematic showing the intrasplenic transplantation of KPN and KPN KF organoids. b Images of liver tumour burden from KPN and KPN KF organoid transplant mice. Representative of six mice per organoid transplant. Scale, 1 cm. c Quantifications of liver tumour burden and tumour number from KPN and two KPN KF (T1 and T2) organoid transplants. (KPN n = 6, 6M, KPN KF T1 n = 7, 7F, KPN KF T2 n = 7, 7F). Data are mean ± s.e.m. Semi-circles include lung metastasis burden. ***P = 0.0006, one-way Mann–Whitney U test. Created with BioRender.com. d Representative HE, CD3, CD8, F4/80 and S100A9 IHC in KPN and KPN KF transplant mice. Representative of six mice per organoid line. Scale, 200 μm. e Quantifications from d KPN KF T1 and T2 with tumour burden represented together as KPN KF. Data are mean ± s.e.m. Representative of KPN n = 6, 6M, KPN KF n = 14, 14F, ****P = 2.5 × 10-5 (Met area); KPN n = 5, 5M, KPN KF n = 7, 7F, **P = 0.0013 (CD3); KPN n = 5, 5M, KPN KF n = 6, 6F, ns, P = 0.2143 (CD8); KPN n = 6, 6M, KPN KF n = 5, 5F, *P = 0.02 (F4/80); KPN n = 5, 5M, KPN KF n = 5, 5F, **P = 0.0079 (S100A9), one-way Mann–Whitney U test. f Schematic model showing the role of wild-type KRAS in KRAS mutant CRC. Loss of wild-type Kras in KPN KF tumours promotes tumour initiation with WNT activation, an enhanced immune infiltrate and blunted metastasis. Created with BioRender.com. Source data are provided as a Source Data file.