Enhancing Breast Cancer Neoadjuvant Therapy Prediction with Proximity Analysis of CD8 + T Cells and Immune Landscape Integration

Abstract

Background: In breast cancer, the spatial relationship between immune and tumor cells is increasingly recognized as critical in determining the efficacy of neoadjuvant therapy (NAT). This study investigated how the distribution of immune cells, particularly CD8⁺ T cells, relative to tumor cells affects treatment outcomes. Methods: Biopsies from 104 breast cancer patients were examined, both pre- and post-NAT, using multiplex immunohistochemistry (mIHC). This study focused on the density and distribution of CD8⁺ T cells, CD68⁺ macrophages, FoxP3⁺ regulatory T cells, and other immune markers. Results: The spatial proximity of CD8⁺ T cells within 20 µm of cancer cells (N20-CD8⁺T) was strongly correlated with improved clinical outcomes across diverse tumor subtypes and NAT regimens. A significant post-NAT decrease in CD4⁺, CD68⁺, and FoxP3⁺ cells highlights notable shifts in the tumor immune landscape. A noteworthy finding was the positive correlation between CXCL9 expression and N20-CD8⁺T cells, suggesting a mechanism for immune cell recruitment and interaction within the tumor microenvironment. These results highlight the complex interplay among NAT, immune cell modifications, and patient outcomes. Conclusions: This study revealed that the proximity of N20-CD8⁺ T cells to tumor cells is consistently associated with favorable NAT outcomes, transcending tumor subtypes, and treatment differences. This highlights the potential of immune cell dynamics, especially CD8⁺ T cells, as predictive biomarkers for therapeutic responses in breast cancer, underscoring their vital role in tumor immunity.