Fig. 6: The non-cell-autonomous role of NF1, TSC1, or TβRII through inflammation and immune regulation. | Nature Communications

Fig. 6: The non-cell-autonomous role of NF1, TSC1, or TβRII through inflammation and immune regulation.

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

Fig. 6: The non-cell-autonomous role of NF1, TSC1, or TβRII through inflammation and immune regulation.The alternative text for this image may have been generated using AI.

A Venn diagram for differential gene expression comparing the primary tumors with sgNf1, sgTsc1, or sgTgfbr2 with controls in Cas9 transgenic mice. Cut-off: FC > 2, P < 0.01. B Heatmap of differentially regulated genes shared by all three primary tumors with sgNf1, sgTsc1, or sgTgfbr2 compared with control tumors. C IPA analysis of 150 genes that are shared among the NF1, TSC1, or TβRII deficient 4T1 tumor cells. D Heat map for major altered immune modulators in 4T1 tumor cells with NF1, TSC1, or TβRII deficiency. The gene names are listed on the right. Red color indicates genes shared among NF1, TSC1, or TβRII deficient cells. E Flow cytometry of various myeloid subsets from primary tumors with NF1, TSC1, and TβRII deficiency vs C1 control, showing % of MDSCs, monocytes, macrophages, cDC1, and cDC2. F Metastatic nodule counts (normalized to tumor weight) upon depletion of Treg or Ly6G cells comparing the Cas9 transgenic vs nude mice that bear TSC1 deficient tumors. Graph shows mean ± s.d. G CODEX imaging of immune cells from primary tumors with NF1, TSC1, or TβRII deficiency. The blue, orange, and pink arrows show LY6G+ neutrophils, CD25+ Tregs, and PD1+ CD8+ T cells, respectively. H CYTEK analysis of primary tumors with NF1, TSC1, or TβRII deficiency. Upper: percentage of CTL, Treg, and Th2; Lower: percentage of PD-1+ in CD8 and CD4 T cells as well as percentage of LAG3+ in CD8, CD44CD8, and Treg cells. Graphs show mean ± s.d. I % of LAG3+ T cells in tumors (n = 4) treated with Tofacitinib. J Metastatic nodule counts (normalized to tumor weight) and tumor weight with Tofacitinib treatment. K Schematic hypothesis showing how NF1, TSC1, or TβRII deficiency leads to altered inflammatory and immune suppressive microenvironment. All graphs show mean ± s.d. Statistical significance was determined by Wald test for (A); two-tailed Student’s t-test for (F) and (H); one-way ANOVA followed by Sidak’s test for (I) and (J). *p < 0.05; **p < 0.01; ***p < 0.001. Exact p-values for (H) are provided in a source data file.

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