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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Spatial Interactions of CD103+ Tissue-Resident Memory T Cells in the Tumor Periphery Are Associated with Clinical
Hyun Lee1, Byung-Kwan Jeong2, Gyungyub Gong2
1Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Purpose:
Triple-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 Methods:
This 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.
Conclusion:
Spatial interaction patterns between CD103+ and other T cell subsets in the tumor periphery influence clinical outcomes in NAC-treated TNBC patients. Analysing such spatial relationships between T cells, rather than their presence alone, may provide additional prognostic information for patients undergoing NAC.

