Fig. 5: Deletion of Nf1, Tsc1, or Tgfbr2 resulted in tumor cell-autonomous inflammatory reprogramming by JAK-STAT3/6. | Nature Communications

Fig. 5: Deletion of Nf1, Tsc1, or Tgfbr2 resulted in tumor cell-autonomous inflammatory reprogramming by JAK-STAT3/6.

From: Loss of tumor suppressors promotes inflammatory tumor microenvironment and enhances LAG3+T cell mediated immune suppression

Fig. 5

A schematic analysis for ATAC and RNA-seq datasets. B RNA-seq Venn diagram showing overlapped genes from in vitro cultured 4T1 cells with sgRNA mediated deletion of Nf1, Tsc1, or Tgfbr2 compared with control 4T1-C1 cells. Cut-off: FC > 1.5, P < 0.05. C ATAC-seq Venn diagram (left) and heatmap (right) showing common differential peaks for all three TS KO vs the control cells. Cut-off: Differential ATAC peaks p < 0.01, FC < −2 and >2. D Increased ATAC peaks for IL6, JAK3 and decreased ATAC peaks for CCL2 that are common for all three TS KO cells, Gapdh as control. E Relative expression (RT-PCR) of IL6, JAK3, IDO1, and CCL2 comparing sgNf1, sgTsc1 or sgTgfbr2 vs control (n = 4). (F) IL6 (n = 3) and IDO1 (n = 3) ELISA (left two panels), JAK3 Western, and CCL2 Cytokine Array and quantitative data (right two panels, IL-23 as control) from sgNf1, sgTsc1 or sgTgfbr2 compared with control. G Western blots of pSTAT3, pSTAT6, pJAK3 and JAK3 comparing sgNf1, sgTsc1 or sgTgfbr2 4T1 cells with C1 control. H RT-PCR of IL6 or IDO1 of cells treated with a pan JAK or a JAK3 specific inhibitor or IL6-neuAb (n = 3). All graphs show mean ± s.d. Average of each biological replicate was plotted, and statistical significance was determined by two-tailed Student’s t-test for (E), (F), and (H). *p < 0.05; **p < 0.01. Exact p-values for (E), (F), and (H) are provided in a source data file.

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