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Background <p>Stereotactic ablative radiotherapy (SABR) is thought to activate T cell responses in patients with cancer, leading to its combination with immunotherapy and chemotherapy for treatment of non-small-cell lung cancer (NSCLC). Here, we aimed to provide a high-resolution transcriptomic profiling of the systemic T cell response following SABR, with or without preceding immunotherapy/chemotherapy.</p> Methods <p>We conducted single-cell RNA and T cell receptor (TCR) sequencing of T cells from peripheral blood of seven patients with early-stage NSCLC taken pre- and post-SABR without or with prior immunotherapy and chemotherapy (icSABR). Other flow cytometry, single-cell RNA-seq data and bulk RNA-seq data were used to validate the results.</p> Results <p>We uncovered distinct T cell response patterns induced by these treatments: while terminal effector CD8<sup>+</sup> T cells showed increased cytotoxic and inhibitory scores, and upregulated immune-activated pathways post-SABR, the reverse responses occurred post-icSABR. Furthermore, the proportion of large T cell clones increased and single clone decreased post-SABR, while the opposite was seen post-icSABR. Of note, both SABR and icSABR largely changed TCR clonotypes, which were mainly large clones post-SABR but single clone post-icSABR, and predominantly from terminal effector CD8<sup>+</sup> T cells and T helper cells, respectively.</p> Conclusions <p>These findings reveal a complex interplay between SABR and immunotherapy, with potentially valuable implications for treatment strategies involving SABR and immunotherapy to induce systemic T cell responses for tumor eradication in patients with NSCLC.</p>

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Pre-immunotherapy alters stereotactic ablative radiotherapy-induced systemic T cell responses in early-stage NSCLC

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月1日

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  • Chao Liu,
  • Yanjuan Chen,
  • Xiaohui Li,
  • Zhijie Bai,
  • Meilin Jiang,
  • Dongsheng Sheng,
  • Wenxue Zou,
  • Rui Huang,
  • Qingyu Huang,
  • Fuhao Wang,
  • Jingyang Zhu,
  • Huiru Sun,
  • Bing Liu,
  • Zongcheng Li,
  • Bing Sun

摘要

Background

Stereotactic ablative radiotherapy (SABR) is thought to activate T cell responses in patients with cancer, leading to its combination with immunotherapy and chemotherapy for treatment of non-small-cell lung cancer (NSCLC). Here, we aimed to provide a high-resolution transcriptomic profiling of the systemic T cell response following SABR, with or without preceding immunotherapy/chemotherapy.

Methods

We conducted single-cell RNA and T cell receptor (TCR) sequencing of T cells from peripheral blood of seven patients with early-stage NSCLC taken pre- and post-SABR without or with prior immunotherapy and chemotherapy (icSABR). Other flow cytometry, single-cell RNA-seq data and bulk RNA-seq data were used to validate the results.

Results

We uncovered distinct T cell response patterns induced by these treatments: while terminal effector CD8+ T cells showed increased cytotoxic and inhibitory scores, and upregulated immune-activated pathways post-SABR, the reverse responses occurred post-icSABR. Furthermore, the proportion of large T cell clones increased and single clone decreased post-SABR, while the opposite was seen post-icSABR. Of note, both SABR and icSABR largely changed TCR clonotypes, which were mainly large clones post-SABR but single clone post-icSABR, and predominantly from terminal effector CD8+ T cells and T helper cells, respectively.

Conclusions

These findings reveal a complex interplay between SABR and immunotherapy, with potentially valuable implications for treatment strategies involving SABR and immunotherapy to induce systemic T cell responses for tumor eradication in patients with NSCLC.