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<p>Tumor-Infiltrating Lymphocytes (TILs) immunotherapy is a highly promising treatment for Non-small Cell Lung Cancer (NSCLC), which is responsible for 18% of all cancer-related deaths. The heterogeneity of TILs remains poorly understood. Here, we utilized combined single-cell RNA (scRNA)/T cell receptor sequencing (scTCR-seq) data from lung adenocarcinoma (LUAD) patients. Naïve CD4<sup>+</sup> and effector memory CD8<sup>+</sup> T cells were increased in tumor tissue compared with circulating blood samples. Activated signaling pathways were detected, and <i>GZMA</i> was identified as a potential novel diagnostic biomarker. During the transitional phase, macrophages (<i>FTL</i>) and dendritic (<i>AIF1</i>) cells transported the most CD3 TCR clones to T cells, while cytotoxicity CD8<sup>+</sup> T (<i>NKG7</i>) cells transported to terminal exhausted CD8<sup>+</sup> T cells. In both transition and expansion phases, T helper cells (<i>CXCL13</i>) are transported to regulatory T cells (Tregs). Additionally, we investigated the expression profiles of key cytokines, checkpoint receptors, and their ligands. Cytotoxicity CD8<sup>+</sup> T cells (<i>CCL5 and IFNG</i>), T helper cells (<i>FTL, TNFRSF4</i>, and <i>TIGIT</i>), and regulatory T cells (<i>CTLA4, TIGIT and FTL</i>) exhibited functional roles in both primary and metastatic tumor stages. Taken together, our study provides a single-cell resolution of the TIL immune landscape and suggests potential treatment strategies to overcome drug resistance.</p>

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Characterizing the immune landscape of tumor-infiltrating lymphocytes in non-small cell lung cancer

  • 期刊论文

  • 发表日期：

    2025年5月5日

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  • Jin-Guo Liu,
  • Lin Yu,
  • Xian-Ling Guo,
  • Xue-Min He,
  • Man Li,
  • Ren-Yuan Gao,
  • Bing-Hui Zhao,
  • Qian-Yu Li,
  • Wen-Jing Zhu,
  • Ping Xu,
  • Xiao-Hua Gu,
  • Yong-An Chen,
  • Xiao-Lan Yin,
  • Yan Shang,
  • Zhen-Hong Guo,
  • Jia-Hao Mao,
  • Yang-Xi Hu,
  • Li-Ming Lu,
  • Jian Hua,
  • Hua Zhang,
  • Yue Li

摘要

Tumor-Infiltrating Lymphocytes (TILs) immunotherapy is a highly promising treatment for Non-small Cell Lung Cancer (NSCLC), which is responsible for 18% of all cancer-related deaths. The heterogeneity of TILs remains poorly understood. Here, we utilized combined single-cell RNA (scRNA)/T cell receptor sequencing (scTCR-seq) data from lung adenocarcinoma (LUAD) patients. Naïve CD4+ and effector memory CD8+ T cells were increased in tumor tissue compared with circulating blood samples. Activated signaling pathways were detected, and GZMA was identified as a potential novel diagnostic biomarker. During the transitional phase, macrophages (FTL) and dendritic (AIF1) cells transported the most CD3 TCR clones to T cells, while cytotoxicity CD8+ T (NKG7) cells transported to terminal exhausted CD8+ T cells. In both transition and expansion phases, T helper cells (CXCL13) are transported to regulatory T cells (Tregs). Additionally, we investigated the expression profiles of key cytokines, checkpoint receptors, and their ligands. Cytotoxicity CD8+ T cells (CCL5 and IFNG), T helper cells (FTL, TNFRSF4, and TIGIT), and regulatory T cells (CTLA4, TIGIT and FTL) exhibited functional roles in both primary and metastatic tumor stages. Taken together, our study provides a single-cell resolution of the TIL immune landscape and suggests potential treatment strategies to overcome drug resistance.