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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月10日

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  • Hongling Liang,
  • Jianqing Huang,
  • Hongsheng Li,
  • Weixing He,
  • Xiang Ao,
  • Zhi Xie,
  • Yu Chen,
  • Zhiyi Lv,
  • Leyao zhang,
  • Yanhua Zhong,
  • Xiaojun Tan,
  • Guodong Han,
  • Jie Zhou,
  • Ni Qiu,
  • Ming Jiang,
  • Haoming Xia,
  • Yongtao Zhan,
  • Lei Jiao,
  • Jie Ma,
  • Derek Radisky,
  • Jia Huang,
  • Xuchao Zhang

摘要

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.