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

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Tumor microenvironment heterogeneity includes diverse stromal cells influencing anti-tumor immunity in breast cancer.
• The functional and spatial interactions of stromal cells with immune cells in breast cancer remain incompletely understood.

Purpose of the Study:

• To investigate the abundance, spatial distribution, and immune cell co-localization of stromal subsets within the breast cancer tumor microenvironment.
• To correlate these stromal and immune features with clinicopathological characteristics and patient outcomes in breast cancer.

Main Methods:

• Multiplex immunofluorescence staining was performed on tumor microarrays from 591 breast cancer patients.
• Analysis focused on the spatial co-localization of distinct stromal and immune cell subsets.
• Correlations with clinicopathological features and patient survival data were assessed.

Main Results:

• Stromal cells exhibited distinct spatial patterns within the tumor microenvironment.
• A perivascular-like stromal subset, disseminated throughout the stroma, was linked to immune-cold regions and T-cell exclusion.
• An inflammatory-like cancer-associated fibroblast subset correlated with the segregation of T cells from cancer cells.

Conclusions:

• Specific stromal cell subsets differentially regulate immune cell infiltration and activation within the breast cancer tumor microenvironment.
• These findings underscore the importance of stromal heterogeneity in shaping anti-tumor immunity and have potential implications for breast cancer patient outcomes.