Fig. 5: Proliferative state delineates spatial cell-cell interactions of the tumor-immune microenvironment in BRCA1/2mut and HRwt tumors.

a A schematic representation of cell-cell spatial interactions significantly enriched (FDR < 0.1) in BRCA1/2mut tumors (n = 31, blue arrows) and in HRwt tumors (n = 13, red arrows). The arrowheads point to the cell type surrounding the cell type denoted by the arrow base. The size of the arrows indicate the FDR-corrected p-value. The dotplot in Fig. S5a denotes the corresponding fold change values. b Representative multiplex immunofluorescence images showing highly proliferating epithelial cells co-localizing with CD8 + T-cells in BRCA1/2mut tumors, and highly proliferating epithelial cells residing further away from CD8 + T-cells in HRwt tumors as shown in a. Experiment was repeated for n = 31 BRCA1/2mut tumors and n = 13 HRwt tumors. c Kaplan-Meier graphs showing high fraction of CD4 + T-cells and d high fraction of CD8 + T-cells neighboring proliferating epithelial cells associate with an improved PFI in patients with BRCA1/2mut tumors. Median was used as a cut-off for high and low fractions. Number of patients at risk is shown at the bottom of each Kaplan-Meier graph. The comparisons between the groups were performed using the log-rank test. e A schematic illustration of functional state and spatial cell-cell interaction analysis. Proliferating epithelial cells were each characterized by their CD4 + T-cell and CD8 + T-cell spatial neighborhood status. Next, Ki67 marker expression was compared in proliferating epithelial cells with different cell-cell spatial neighborhoods in BRCA1/2mut and HRwt tumors separately. f Violin plots showing the probability densities of Ki67 expression in proliferating epithelial cells in the different CD8 + T-cell neighborhood and HR-groups. g Violin plots showing the probability densities of Ki67 expression in proliferating epithelial cells in the different CD4 + T-cell neighborhood and HR-groups. In the box plots inside violin plots the black horizontal lines represent the sample medians, the boxes extend from first to third quartile and whiskers indicate values at 1.5 times the interquartile range. Two-sided wilcoxon rank-sum test was used for pairwise comparisons. Source data are provided with the paper.