Stromal Cell Subsets Modulate T-cell Infiltration in Early Breast Cancer

Recent studies of the tumor microenvironment (TME) have elucidated the heterogeneity of stromal cells, with increasing evidence suggesting that stromal subsets play an important role in regulating antitumor immunity in breast cancer. However, the functional diversity of these cells within the tumor-immune microenvironment and how they interact with immune cells in a spatial and clinical context remain poorly understood. We performed multiplex immunofluorescence on tumor microarrays from two cohorts consisting of 591 patients with breast cancer to assess the abundance and spatial co-localization of stromal and immune subsets and their correlation with clinicopathologic features and patient outcomes. We found that stromal cells were spatially distinct. A perivascular-like subset that was disseminated throughout the stroma rather than restricted to vessel-adjacent regions was enriched in an immune-cold environment and associated with T-cell exclusion. An inflammatory-like cancer-associated fibroblast subset was associated with segregation of T cells from cancer cells. Our findings highlight the differential impact of stromal subsets on immune infiltration and activation within the breast cancer TME with potential implications for patient outcomes. SIGNIFICANCE: This study characterized spatially defined interactions between stromal and immune subsets in large clinical cohorts of early breast cancer. Findings from this study will fill gaps in current knowledge in how diverse stromal cell subsets, particularly novel subsets, interact with immune cells in a clinically relevant context.