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<p>Gemcitabine and cisplatin (GP) serve as first-line induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC), yet predictive markers are lacking. Here we performed multi-omics profiling, including proteomics, phosphoproteomics, genomics and transcriptomics, on 240 patients with NPC who were receiving GP-IC or concurrent chemoradiotherapy (CCRT) alone. Through multi-omic integration, we identified three proteomic subtypes with distinct therapeutic vulnerabilities. The S1 subtype showed a predominant interferon-γ response and had favorable outcomes with CCRT alone. The S2 subtype featured copy-number-driven cell cycle activation, deriving benefits from GP-IC. The immune-exhausted S3 subtype exhibited high IgA<sup>+</sup> plasma cell infiltration and was resistant to GP-IC but responded to anti-PD-1 therapy. Single-cell RNA sequencing confirmed interaction between IgA<sup>+</sup> plasma cells and CD8<sup>+</sup> T cells in nonresponders. Validation from three phase III trials and spatial analyses demonstrated that high IgA<sup>+</sup> plasma cell infiltration predicted GP-IC resistance but benefited from anti-PD-1 therapy. This study delineates a subtype-specific landscape of GP-IC response and may inform personalized treatment in NPC.</p>

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Multi-omic characterization of nasopharyngeal carcinoma delineates the subtype-specific landscape of response to induction chemotherapy

  • 期刊论文

  • 发表日期：

    2026年4月15日

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  • Yingqin Li,
  • Dongxue Wang,
  • Chunxian Ou,
  • Zaoqu Liu,
  • Xianfeng Shao,
  • Yuheng Zhao,
  • Xinxin Zhang,
  • Jiaxi Shen,
  • Qingmei He,
  • Xu Liu,
  • Yuan Zhang,
  • Xiaoyu Liang,
  • Yaoyi Li,
  • Huimin Huang,
  • Linhai Xie,
  • Gaoyuan Wang,
  • Yelin Liang,
  • Kaixuan Li,
  • Meng Yan,
  • Qianying Yang,
  • Linglong Tang,
  • Lei Chen,
  • Yin Zhao,
  • Sha Xu,
  • Ying Sun,
  • Jia-Xing Yue,
  • Na Liu,
  • Aihua Sun,
  • Jun Ma,
  • Fuchu He

摘要

Gemcitabine and cisplatin (GP) serve as first-line induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC), yet predictive markers are lacking. Here we performed multi-omics profiling, including proteomics, phosphoproteomics, genomics and transcriptomics, on 240 patients with NPC who were receiving GP-IC or concurrent chemoradiotherapy (CCRT) alone. Through multi-omic integration, we identified three proteomic subtypes with distinct therapeutic vulnerabilities. The S1 subtype showed a predominant interferon-γ response and had favorable outcomes with CCRT alone. The S2 subtype featured copy-number-driven cell cycle activation, deriving benefits from GP-IC. The immune-exhausted S3 subtype exhibited high IgA+ plasma cell infiltration and was resistant to GP-IC but responded to anti-PD-1 therapy. Single-cell RNA sequencing confirmed interaction between IgA+ plasma cells and CD8+ T cells in nonresponders. Validation from three phase III trials and spatial analyses demonstrated that high IgA+ plasma cell infiltration predicted GP-IC resistance but benefited from anti-PD-1 therapy. This study delineates a subtype-specific landscape of GP-IC response and may inform personalized treatment in NPC.