Fig. 4

Tumor cell extrinsic factors underlying treatment resistance to tipifarnib. a tSNE plot of non-tumor mouse cells (dots) from PDX of BC159-T#3, color-coded by cluster, circled by global cell type. b tSNE plot, color-coded by sample origin and circled by cell type (top panel). Relative cellular composition of non-tumor mouse cells treated with tipifarnib or vehicle (bottom panel). c tSNE plot (top panel) and relative cellular composition (bottom panel) of fibroblasts from PDX mouse cells treated with tipifarnib or vehicle, color-coded by cluster (top left panel) or sample origin (top middle and right panel). d Volcano plot of differentially expressed genes in mouse fibroblasts from PDX treated with tipifarnib or vehicle. Genes with fold change > 0.8 with P < 0.001 are colored in red. e Validation of relative overexpression of Igfbp7 and Mdk in mouse cancer-associated myofibroblasts (MyoCAFs, ACTA2 positive) from the tipifarnib group compared to those from the vehicle group by immunohistochemistry staining. Scale bar, 100 μm. f Increased infiltration of mouse macrophages (CD68 positive) in PDXs treated with tipifarnib confirmed by immunohistochemistry staining. Scale bar, 100 μm. g tSNE plot (top panel) and relative cellular composition (bottom panel) of mouse macrophages from PDX treated with tipifarnib or vehicle, color-coded by cluster (top left panel) and sample origin (top middle and right panel). h Volcano plot of differentially expressed genes between vehicle and tipifarnib-treated mouse macrophages from PDX. Genes with fold change > 0.8 with P < 0.001 are colored in red. i tSNE plot (top panel) and relative cellular composition (bottom panel) of mouse lymphocytes from PDX treated with tipifarnib or vehicle, color-coded by cluster (top left panel) and sample origin (top middle and right panel). j Volcano plot of differentially expressed genes between vehicle and tipifarnib-treated mouse T cells from PDX. Genes with fold change > 0.8 with P < 0.001 are colored in red. k Increased infiltration of mouse T cells (CD8 positive) in PDX treated with tipifarnib confirmed by immunohistochemistry staining. Scale bar, 100 μm