Spatial Interactions of CD103+ Tissue-Resident Memory T Cells in the Tumor Periphery Are Associated with Clinical Outcomes in Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy

PurposeTriple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis.CD103+ tissue-resident memory T (TRM) cells are crucial for anti-tumor immunity in TNBC.We investigated whether their spatial interactions with other T-cells influence clinical outcomes, particularly following neoadjuvant chemotherapy (NAC). Materials and MethodsThis retrospective study analyzed 182 TNBC patients (98 NAC-treated; 84 non-NAC).Using Opal multiplex immunohistochemistry data and the Spatial Image Analysis of Tissues (SPIAT) R package, we analysed spatial interactions between CD103+ cells and other T cell subsets (CD45RO, CD8, CD4, PD-1) in central/peripheral tumor regions.Normalized mixing score (NMS) quantified spatial interactions. Results NMS-based clustering revealed two distinct CD103+ cell interaction patterns-Cluster 1 (low NMS) characterized by weaker and Cluster 2 (high NMS) by stronger spatial interactions between CD103+ and other T cell subsets.In the NAC group, Cluster 2 in the tumor periphery was associated with lower pathologic stage (p=0.002),higher stromal tumor-infiltrating lymphocyte level (p=0.031), and significantly improved recurrence-free survival (p=0.028) and overall survival (p=0.018)compared to Cluster 1. Central tumor region clustering patterns had no association with prognosis.No significant survival-related differences were observed in the non-NAC group according to NMS-based clustering. ConclusionSpatial interaction patterns between CD103+ and other T cell subsets in the tumor periphery