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<p>Cancer metastasis accounts for the majority of cancer-related deaths and lymph node metastasis is critical in cancer staging and prognosis. However, the mechanisms involved in lymph node metastatic non-small cell lung cancer (NSCLC) remain unclear. Here, we delineate the cellular and spatial landscape of metastatic lymph nodes and their matched primary tumors in NSCLC using multimodal omics. In results, tumor core and peripheral regions respectively exhibit high stemness and elevated expression of immunoglobulins. Increased expressions of <i>CD274</i> (PD-L1) are observed in the immunoglobulin-high malignant cells and <i>SPP1</i>+<i>IFI30</i>+ macrophages. Notably, residual and tertiary lymphoid structures are identified. However, their anti-tumor immunity is compromised by <i>CXCL13</i>+ T cell exhaustion and immune exclusion. Furthermore, we identify the ferroptosis signaling, with its key factor FTH1 showing strong associations with cancer cell stemness and metastasis. This study elucidates the mechanisms of metastasis and immune evasion in lymph node metastatic NSCLC, providing insights for targeted therapies.</p>

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Dissecting origin factors of lymph node metastasis in non-small cell lung cancer via multimodal omics

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月13日

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  • Di Chen,
  • Yu Liu,
  • Daiwang Shi,
  • Siyi Li,
  • Yawei Wang,
  • Qiuping Wang,
  • Tingze Feng,
  • Shaojun Pei,
  • Yuhan Wang,
  • Yi Zhang,
  • Xiang Shi,
  • Ziqiang Hong,
  • Jinghan Li,
  • Zhanwu Yu,
  • Nan Sun,
  • Wei Wang,
  • Liang Zhang,
  • Yegang Ma,
  • Hai-long Piao,
  • Hong-Xu Liu

摘要

Cancer metastasis accounts for the majority of cancer-related deaths and lymph node metastasis is critical in cancer staging and prognosis. However, the mechanisms involved in lymph node metastatic non-small cell lung cancer (NSCLC) remain unclear. Here, we delineate the cellular and spatial landscape of metastatic lymph nodes and their matched primary tumors in NSCLC using multimodal omics. In results, tumor core and peripheral regions respectively exhibit high stemness and elevated expression of immunoglobulins. Increased expressions of CD274 (PD-L1) are observed in the immunoglobulin-high malignant cells and SPP1+IFI30+ macrophages. Notably, residual and tertiary lymphoid structures are identified. However, their anti-tumor immunity is compromised by CXCL13+ T cell exhaustion and immune exclusion. Furthermore, we identify the ferroptosis signaling, with its key factor FTH1 showing strong associations with cancer cell stemness and metastasis. This study elucidates the mechanisms of metastasis and immune evasion in lymph node metastatic NSCLC, providing insights for targeted therapies.