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<p>Radiotherapy resistance and immune evasion are prominent features of recurrent nasopharyngeal carcinoma (rNPC). However, their mechanisms remain incompletely understood. Here, we conducted single-cell and spatial transcriptomics analysis of 39 tumors from 24 patients to reveal the microenvironmental differences between primary and rNPC. Specific MCAM<sup>+</sup> cancer-associated fibroblasts are significantly enriched in rNPC, where they promote tumor radioresistance through the collagen IV–ITGA2–FAK–AKT axis. Furthermore, we found that collagen IV suppresses the infiltration of T cells, and we identified mechanisms of immune escape in rNPC. We uncovered the presence and function of CD8 ZNF683 cells in rNPC with lower cytotoxicity. The abundance of B cells and tertiary lymphoid structures significantly diminishes in rNPC. Finally, we confirmed that CD47–SIRPα commonly existed between myeloid and malignant cells in rNPC. This study provides an in-depth understanding of the mechanism of radioresistance and immune evasion in rNPC as well as highlighting critical preliminary targets for curing rNPC.</p>

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Single-cell and spatial transcriptomics reveal mechanisms of radioresistance and immune escape in recurrent nasopharyngeal carcinoma

  • 期刊论文

  • 发表日期：

    2025年7月21日

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  • Rui You,
  • Qunlun Shen,
  • Chao Lin,
  • Kangning Dong,
  • Xiao Liu,
  • Hanshi Xu,
  • Wanming Hu,
  • Yulong Xie,
  • Ruoqi Xie,
  • Xiaoyi Song,
  • Chunliu Huang,
  • Jinhui Wu,
  • Tao Yu,
  • Huifeng Li,
  • Zining Wang,
  • Keming Chen,
  • Xiong Zou,
  • Peiyu Huang,
  • Yijun Hua,
  • Youping Liu,
  • Tianliang Xia,
  • Shihua Zhang,
  • Mingyuan Chen

摘要

Radiotherapy resistance and immune evasion are prominent features of recurrent nasopharyngeal carcinoma (rNPC). However, their mechanisms remain incompletely understood. Here, we conducted single-cell and spatial transcriptomics analysis of 39 tumors from 24 patients to reveal the microenvironmental differences between primary and rNPC. Specific MCAM+ cancer-associated fibroblasts are significantly enriched in rNPC, where they promote tumor radioresistance through the collagen IV–ITGA2–FAK–AKT axis. Furthermore, we found that collagen IV suppresses the infiltration of T cells, and we identified mechanisms of immune escape in rNPC. We uncovered the presence and function of CD8 ZNF683 cells in rNPC with lower cytotoxicity. The abundance of B cells and tertiary lymphoid structures significantly diminishes in rNPC. Finally, we confirmed that CD47–SIRPα commonly existed between myeloid and malignant cells in rNPC. This study provides an in-depth understanding of the mechanism of radioresistance and immune evasion in rNPC as well as highlighting critical preliminary targets for curing rNPC.