Spatial Architecture of Single-Cell and Vasculature in Tumor Microenvironment Predicts Clinical Outcomes in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options, which warrants the identification of novel therapeutic targets. Deciphering nuances in the tumor microenvironment (TME) may unveil insightful links between anti-tumor immunity and clinical outcomes, yet such connections remain underexplored. Here we employed a dataset derived from imaging mass cytometry of 71 TNBC patient specimens at single-cell resolution and performed in-depth quantifications with a suite of multi-scale computational algorithms. The TNBC TME reflected a heterogeneous ecosystem with high spatial and compositional heterogeneity. Spatial analysis identified ten recurrent cellular neighborhoods (CNs) - a collection of local TME characteristics with unique cell components. The prevalence of CNs enriched with B cells, fibroblasts, and tumor cells, in conjunction with vascular density and perivasculature immune profiles, could significantly enrich for long-term survivors. Furthermore, relative spatial colocalization of SMA