中山大学陈明远小组的研究显示，单细胞和空间转录组学揭示复发性鼻咽癌放射耐药和免疫逃逸的机制。相关论文发表在2025年7月21日出版的《自然—遗传学》杂志上。

课题组人员对来自24例患者的39个肿瘤进行了单细胞和空间转录组学分析，以揭示原发性和rNPC之间的微环境差异。特异性MCAM⁺癌症相关成纤维细胞在rNPC中显著富集，它们通过胶原IV-ITGA2-FAK-AKT轴促进肿瘤放射抵抗。

此外，研究组发现IV型胶原抑制T研究组确定了rNPC的免疫逃逸机制。该课题组研究人员发现CD8 ZNF683细胞在rNPC中的存在和功能具有较低的细胞毒性。B的丰度细胞和三级淋巴结构在rNPC中显著减少。最后，该课题组人员证实了CD47-SIRPα在rNPC的髓细胞和恶性细胞之间普遍存在。本研究深入了解了rNPC的辐射耐药和免疫逃避机制，并强调了治疗rNPC的关键初步靶点。

研究人员表示，放疗抵抗和免疫逃避是复发性鼻咽癌（rNPC）的显著特征。然而，它们的机制仍然不完全清楚。

附：英文原文

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

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

Issue&Volume: 2025-07-21

Abstract: 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 Tcells, 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 Bcells 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.

DOI: 10.1038/s41588-025-02253-8

Source: https://www.nature.com/articles/s41588-025-02253-8