Fig. 5: Gain of basal cytokeratin expression is associated with enhanced immune activation in ESR1 mutant tumors.

a Venn diagrams showing the intersection of significantly enriched hallmark pathways in three sets of comparisons: BCK-high vs low in 1) TCGA ER+ tumors (n = 202 in each group), 2) METABRIC ER+ tumors (n = 376 in each group) and 3) ESR1 mutant (n = 7) vs. WT (n = 44) metastatic tumors. BCKs high and low were defined by the upper and bottom quartiles of each subset. The seven overlapping pathways are shown in a frame, and immune-related pathways are highlighted in red. b Immune scores based on ESTIMATE evaluations in basal tumors (METABRIC n = 328; TCGA n = 190), BCK-high (METABRIC n = 376; TCGA n = 202) and low (METABRIC n = 376; TCGA n = 202) subsets of ER+ tumors. Box plots span the upper quartile (upper limit), median (center) and lower quartile (lower limit). Whiskers extend a maximum of 1.5× IQR. Mann–Whitney U-test (two-sided) was used for comparison. c Lymphocytes and leukocyte fractions⁶⁷ comparisons among TCGA basal subtype tumors (n = 161), ER+ BCK-high (n = 163) and low (n = 179) tumors. Box plots span the upper quartile (upper limit), median (center) and lower quartile (lower limit). Whiskers extend a maximum of 1.5× IQR. Mann–Whitney U-test (two-sided) was applied. d Kaplan–Meier plots showing the disease-specific survival (DSS) (METABRIC) and overall survival (OS) (TCGA) comparing patients with ER+ BCKs high vs. low tumors. Censored patients were labeled in cross symbols. Log-rank test (two-sided) was used and hazard ratio with 95% CI were labeled. e Immune scores based on ESTIMATE evaluations in ESR1 mutant (n = 7) and WT metastatic (n = 44) lesions. Box plots span the upper quartile (upper limit), median (center) and lower quartile (lower limit). Whiskers extend a maximum of 1.5× IQR. Mann–Whitney U-test (two-sided) was used. f Dot plot showing the enrichment level alterations of immune cell subtypes in ESR1 mutant metastatic lesions using Davoli⁶⁸ and Tamborero⁶⁹ signatures between ESR1 mutant (n = 7) and WT (n = 44) tumors. Significantly increased immune cell subtypes in ESR1 mutant tumors were labeled in red (p < 0.05). Source data are provided as a Source Data file for b–f.