Spatial proximity of CD8+ T cells to tumor cells predicts neoadjuvant therapy efficacy in breast cancer.

Abstract

The spatial proximity of CD8⁺ T cells to tumor cells critically influences the efficacy of neoadjuvant therapy (NAT) in breast cancer (BC). In this study, we evaluated whether the presence of CD8⁺ T cells and other immune cells near cancer cells predicts treatment outcomes across various BC subtypes. We analyzed pre- and post-NAT biopsies from 104 BC patients using multiplex immunofluorescence (mIF) and immunohistochemistry (IHC) to assess the distribution of immune markers, including CD8⁺ T cells, CD68⁺ macrophages, FoxP3⁺ regulatory T cells. Our findings revealed that a higher percentage of CD8⁺ T cells within 20 µm of cancer cells (N20-CD8⁺ T cells) was strongly correlated with improved pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS), regardless of tumor subtype or NAT regimen. Moreover, a positive correlation between CXCL9 expression and N20-CD8⁺ T cells suggests that CXCL9 may facilitate the recruitment of CD8⁺ T cells to tumor cells. Our study emphasizes the link between immune cell composition and location, and patient outcomes with NAT. Focusing on the spatial dynamics of CD8⁺ T cells could significantly advance personalized treatment strategies and the development of targeted immunotherapies in BC.