Spatial proximity of CD8+ T cells to tumor cells predicts neoadjuvant therapy efficacy in breast cancer
Hongling Liang, Jianqing Huang, Hongsheng Li, Weixing He, Xiang Ao, Zhi Xie, Yu Chen, Zhiyi Lv, Leyao Zhang, Leyao zhang, Xiaojun Tan, Guodong Han, Jie Zhou, Ni Qiu, Ming Jiang, Haoming Xia, Yongtao Zhan, Lei Jiao, Jie Ma, Derek C. Radisky, Jia Huang, Xu‐Chao Zhang, Jia Huang, Xu‐Chao Zhang
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.