(A) Example tissue colored by number of CD3 T cell neighbors of each cell. Tumor in orange. (B and C) Recurrence-free survival (RFS) of patients who are ER⁺ stratified by stromal neighbors of epithelial (B) or overall survival (OS) of patients with TNBC stratified by immune neighbors of immune (C) in the discovery (left) and validation (right) cohorts. (D) Multivariable CPH modeling of (left) RFS of patients who are ER⁺ for stromal neighbors of epithelial or (right) OS of patients TNBC for immune neighbors of immune. (E and G) RFS of patients with TNBC stratified by macrophage neighbors of tumor (E) or B cell neighbors of T cells (G) in the discovery (left) and validation (right) cohorts. (F and H) Multivariable CPH modeling of RFS of patients with TNBC for macrophage neighbors of tumor (F) or CD20 B cell neighbors of CD3 T cells (H). (I) TNBC OS stratified by tumor-immune mixing score in MIBI (top) and validation cohorts (i.e., CycIF and IMC; bottom). (I) TNBC OS stratified by occupancy AUC of T (left) or B lymphocytes (right). (K) Multivariable CPH modeling of T (left) and B lymphocyte (right) occupancy AUC. (L) TNBC OS stratified by fractal dimension slope difference for T (top) or B lymphocytes (bottom). (M) Top: Representative tissue showing nuclei (blue) and PD-1 (red). Scale bar: 130 μm. Bottom: Voronoi tessellation of tissue; all cells (blue), PD-1⁺ cells (red), and interactions (black line). (N) OS of CycIF TNBC patients stratified by PD-1 interactions. Bottom: CPH modeling of PD-1 interaction metric. (A–N) Kaplan-Meier P values from log-rank test; validation cohort FDR corrected with the Benjamini-Hochberg method. CPH modeling P values for spatial variable given in panel titles; HR estimates are marked by boxes, and data are shown as 95% CI. (A–H) Neighbors are within a 40 μm radius. (J–L) Includes lymphocytes within 20 μm of tumor.