Spatial proximity of CD8+ T cells to tumor cells predicts neoadjuvant therapy efficacy in breast cancer
The spatial proximity of CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T cells, CD68<sup>+</sup> macrophages, FoxP3<sup>+</sup> regulatory T cells. Our findings revealed that a higher percentage of CD8<sup>+</sup> T cells within 20 µm of cancer cells (N20-CD8<sup>+</sup> 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<sup>+</sup> T cells suggests that CXCL9 may facilitate the recruitment of CD8<sup>+</sup> 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<sup>+</sup> T cells could significantly advance personalized treatment strategies and the development of targeted immunotherapies in BC.
Authors
- Leyao Zhang (ORCID: https://orcid.org/0009-0001-3720-3130)
- Haoming Xia (ORCID: https://orcid.org/0000-0001-9906-4466)
- Ming Jiang (ORCID: https://orcid.org/0000-0002-1927-5667)
- Xiang Ao
- Ni Qiu (ORCID: https://orcid.org/0000-0002-7191-5545)
- Derek C. Radisky (ORCID: https://orcid.org/0000-0002-1962-8784)
- Zhi Xie (ORCID: https://orcid.org/0000-0002-5589-4836)
- Yongtao Zhan
- Zhiyi Lv (ORCID: https://orcid.org/0000-0002-1687-4277)
- Xu‐Chao Zhang (ORCID: https://orcid.org/0000-0002-4138-8115)
- Weixing He
- Yu Chen (ORCID: https://orcid.org/0000-0002-0171-3884)
- Hongsheng Li (ORCID: https://orcid.org/0000-0003-3749-9055)
- Jianqing Huang
- Jie Zhou (ORCID: https://orcid.org/0009-0006-7384-3561)
- Lei Jiao (ORCID: https://orcid.org/0000-0001-7568-0328)
- Jie Ma (ORCID: https://orcid.org/0000-0002-5729-1297)
- Guodong Han (ORCID: https://orcid.org/0000-0003-4249-4507)
- Xiaojun Tan (ORCID: https://orcid.org/0000-0002-3088-8149)
- Hongling Liang (ORCID: https://orcid.org/0000-0001-5474-7888)
- Jia Huang
- Yanhua Zhong
Institutions
- Jacksonville College (US)
- Guangdong Academy of Medical Sciences (CN)
- Mayo Clinic in Florida (US)
- Guangdong Provincial People's Hospital (CN)
- Southern Medical University (CN)
- South China University of Technology (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2025-02-10
- DOI
- https://doi.org/10.1038/s41523-025-00728-9
- Citations
- 18
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 18.82
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province