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<p>Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality, and therapies utilizing tumor-infiltrating lymphocytes (TILs) show significant promise. However, molecular signatures defining a productive TIL-mediated response remain poorly characterized. Here, we establish a patient-derived organoid and autologous TIL co-culture platform to show that expanded TILs mediate potent, specific cytotoxicity against NSCLC organoids. This functional response is associated with a crucial shift in T-cell states from proliferative towards effector memory phenotypes and involves activating key signaling networks, including the TNF and IL-17 pathways. Furthermore, T-cell receptor (TCR) analysis confirms the expansion process selectively enriches tumor-associated clonotypes, resulting in a more focused repertoire. This work delineates the transcriptional and clonal signatures of an effective anti-tumor immune response, providing a robust framework to guide next-generation personalized TIL therapies.</p>

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Transcriptome profiling of tumor-infiltrating lymphocyte-mediated cytotoxicity against patient-derived lung cancer organoids

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月23日

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  • Ziwen Qin,
  • Hongchang Zhang,
  • Yanling Li,
  • Jianyi Yang,
  • Haozhen Liu,
  • Zhuojue Guan,
  • Qinghua Hou,
  • Haocheng Du,
  • Xiaoqiang Li,
  • Xian Lin,
  • Qumiao Xu,
  • Qiao Li,
  • Junhui Chen,
  • Jixian Liu,
  • Chao Chen

摘要

Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality, and therapies utilizing tumor-infiltrating lymphocytes (TILs) show significant promise. However, molecular signatures defining a productive TIL-mediated response remain poorly characterized. Here, we establish a patient-derived organoid and autologous TIL co-culture platform to show that expanded TILs mediate potent, specific cytotoxicity against NSCLC organoids. This functional response is associated with a crucial shift in T-cell states from proliferative towards effector memory phenotypes and involves activating key signaling networks, including the TNF and IL-17 pathways. Furthermore, T-cell receptor (TCR) analysis confirms the expansion process selectively enriches tumor-associated clonotypes, resulting in a more focused repertoire. This work delineates the transcriptional and clonal signatures of an effective anti-tumor immune response, providing a robust framework to guide next-generation personalized TIL therapies.