Fig. 1: “Cold” TNBC show higher rates of engraftment in PDX models in contrast to immune enriched “Hot” TNBCs. | npj Breast Cancer

Fig. 1: “Cold” TNBC show higher rates of engraftment in PDX models in contrast to immune enriched “Hot” TNBCs.

From: Immunologically “cold” triple negative breast cancers engraft at a higher rate in patient derived xenografts

Fig. 1

a Bulk expression of immune genes in TCGA TNBC. Heatmap of the bulk expression of immune gene markers in hot and cold TNBC TCGA tumors (red bars and blue bars respectively). b Immune proportions in TCGA TNBC. Proportions of M2 macrophages (top left), T-regs (top right), M1 macrophages (bottom left), and non-T-reg CD4 T-cells (bottom right) in hot and cold TCGA TNBC tumors (red bars and blue bars respectively). T-tests were used to investigate the differences between hot and cold TNBC samples, and enter lines in the boxplots indicate the median. The bounds of the box indicate the first to third quartile values, while the bounds of the lower and upper whiskers indicate the smallest observation greater than or equal to the first quartile −1.5 times the inter-quartile range and the largest observation smaller or equal to the third quartile +1.5 times the inter-quartile range respectively. c Matching the PDX cancer cell profiles to the deconvoluted TCGA cancer cell profiles. 94% of the PDX models match the cold cancer cell profile. The histogram shows the frequency of the ratios of each model’s correlation the cold cancer cell profile vs the hot cancer cell profile. The bars in red (left) indicate that the hot cancer cell profile was the best match, while the bars in blue (right) indicate that the cold cancer cell profile was the best match. d Bulk expression of immune genes in patient tumors. Heatmap of bulk expression of immune cell markers in the HCI tumors that did not engraft in PDXs vs those that did (blue and red bars respectively). e Immune proportions in patient tumors. Proportions of M2 macrophages (top left), T-regs (top right), M1 macrophages (bottom left), and non-T-reg CD4 T-cells (bottom right) in hot and cold TCGA TNBC tumors (red bars and blue bars respectively). T-tests were used to investigate the differences between TNBCs that engrafted in murine models and those that did not. Center lines in the boxplots indicate the median, and the bounds of the box indicate the first to third quartile values. The bounds of the lower and upper whiskers indicate the smallest observation greater than or equal to the first quartile −1.5 times the inter-quartile range and the largest observation smaller or equal to the third quartile +1.5 times the inter-quartile range respectively. f Immune State. M2 macrophages release exosomes that include miR-29a-3p and miR-21-5p that reprogram T-cells to T-regs. Conversely, Tregs then release interleukins including IL-10, IL-4 and IL-13 that then reprogram M1 to M2 macrophages. The presence of T-regs and M2 macrophages leads to a cancer promoting tumor state.

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