Figure 4.

TNBC cells in the inflamed state are chemoresistant. (a) ISG module scores from a panel of 84 breast cancer cell lines were correlated with drug sensitivity values across 90 compounds. Sorted Pearson correlation values shown with a cutoff for significant (p = 0.05) correlations indicated by a dashed line. (b) Scatter plot of ISG module scores in breast cancer cell lines compared with their sensitivity (normalized –log of IC₅₀) to gemcitabine. P value based on Pearson correlation. (c) Proliferation of HCC38 HLA^HI (top 5%), HLA^LO (bottom 10%), and bulk population in response to 72 h gemcitabine treatment compared to DMSO control. IC₅₀ quantification of dose–response curves shown to the right. (d) Fold change in apoptotic cells in HCC38 HLA subpopulations after 72 h treatment with the IC₅₀ dose (5 nM) of gemcitabine normalized to DMSO control. (e) Proliferation of MDA-MB-468 HLA^HI, HLA^LO and bulk populations in response to 72 h gemcitabine treatment compared to DMSO control. IC₅₀ quantification of dose–response curves shown to the right. (f) Fold change in apoptotic cells in MDA-MB-468 HLA subpopulations after 72 h treatment with the IC₅₀ dose (7.8 nM) of gemcitabine normalized to DMSO control. (g) Fold change in the number of cells remaining for HCC38(left) and MDA-MB-468 (right) samples treated for the indicated time period with 2.5 nM or 11 nM gemcitabine relative to day 0 calculated for n = 8 independent samples. For comparison, the mean day 0 cell count from n = 4 independent samples was used. (h) Representative images of colony formation assay for HCC38 (top) and MDA-MB-468 (top) HLA^LO (left), bulk (middle), and HLA^HI (right) cells following chemotherapy treatment. Cells were stained with Hoechst 33,342 and fluorescent image inverted for clarity. Scale bar, 200 µm. For (c–f), data represents n = 4 biologically independent samples. Error bars are mean ± s.d., and P values calculated using a two-sided t-test except for (g) in which a two-sided t-test with Welch’s correction was used.