Fig. 4: Mutational signatures as determinants of immunophenotypes.

a, Differences in kernel density estimates in UMAP space for pairwise comparisons of mutational signatures. b, Estimated effects of mutational signature and anatomical site on T and NK cell cluster composition based on a GLM, with models fitted excluding ascites samples. The colour gradient indicates the log₂-transformed odds ratio (red, enrichment; blue, depletion), and sizes indicate the Bonferroni-corrected –log₁₀(P value). c, Distributions of CD8⁺ T cell state module scores and JAK–STAT signalling pathway activity scores with respect to mutational signature (patient counts shown). d, Scaled module scores within the subset of CD8⁺ T cells with respect to pseudotime and mutational signature. e, Correlation of JAK–STAT signalling scores in CD8⁺ T cells in CD45⁺ samples with those in cancer cells in matched CD45⁻ samples. f, Left, intra-sample diversity of T and NK cell clusters in adnexal and non-adnexal samples estimated by Shannon entropy, with samples grouped by mutational signature (patient and sample counts shown). Right, intra- and inter-patient dissimilarity in T and NK cell cluster composition, with samples grouped by mutational signature, estimated using the Bray–Curtis distance. Pairwise dissimilarity is shown for all pairs of sites (patient and sample pair counts shown) excluding ascites (top) and for adnexal versus non-adnexal pairs of sites (bottom). g, Spatial density of CD8⁺ T cell phenotypes in adnexal and non-adnexal mpIF samples as a function of distance to the tumour–stroma interface, with samples grouped by mutational signature (Methods). In c and f, box plots and violin plots show the median, top and bottom quartiles; whiskers correspond to 1.5× IQR. Colours in f and g are analogous to those in c–e. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; brackets indicate two-sided Wilcoxon pairwise comparisons in c and f.