Scholarlink

Background <p>Neoadjuvant immune checkpoint blockade (NA-ICB) shows promise in treating resectable and locally advanced non-small cell lung cancer (NSCLC), yet the specific T cell subtypes that expand and become functionally reactivated remain incompletely characterised.</p> Methods <p>We applied single-cell RNA sequencing, TCR repertoire analysis, and flow cytometry to tumour, paired normal lung tissue, and peripheral blood samples from 26 NA-ICB-treated and 14 treatment-naïve NSCLC patients to investigate responsive T cell subtypes, their tissue origins, migration patterns, and phenotype transitions.</p> Results <p>CD8 + CX3CR1 + T cells were significantly enriched in responsive tumours, as evidenced by increased proportions (<i>p</i> = 0.0027) and clonal expansion in scRNA-seq, and elevated protein-level frequencies detected by flow cytometry (<i>p</i> = 0.021). Longitudinal analysis revealed proliferation of these cells in peripheral blood post-treatment. Shared TCR clonotypes were identified across blood and tumour samples. Pseudotime analysis indicated differentiation of these cells into exhausted and cytotoxic NK-like CD8 + T cells upon tumour infiltration.</p> Conclusion <p>These findings suggest that CD8 + CX3CR1 + T cells may represent circulating cytotoxic precursors associated with effective NA-ICB responses, suggesting their potential as predictive biomarkers and therapeutic targets for adoptive cell therapy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Systemic activation and tissue infiltration of CD8 + CX3CR1 + T cells in non-small cell lung cancer treated with neoadjuvant immune checkpoint blockade

  • 期刊论文

  • 发表日期：

    2025年11月22日

查看全文
  • Sisi Dai,
  • Yongcheng Liu,
  • Tingting Guo,
  • Hong Luo,
  • Guanglei Yang,
  • Songliang Yu,
  • Sifan Zhang,
  • Lili Jiang,
  • Jie Liu,
  • Ye Wang,
  • Daxing Zhu,
  • Xuyu Cai

摘要

Background

Neoadjuvant immune checkpoint blockade (NA-ICB) shows promise in treating resectable and locally advanced non-small cell lung cancer (NSCLC), yet the specific T cell subtypes that expand and become functionally reactivated remain incompletely characterised.

Methods

We applied single-cell RNA sequencing, TCR repertoire analysis, and flow cytometry to tumour, paired normal lung tissue, and peripheral blood samples from 26 NA-ICB-treated and 14 treatment-naïve NSCLC patients to investigate responsive T cell subtypes, their tissue origins, migration patterns, and phenotype transitions.

Results

CD8 + CX3CR1 + T cells were significantly enriched in responsive tumours, as evidenced by increased proportions (p = 0.0027) and clonal expansion in scRNA-seq, and elevated protein-level frequencies detected by flow cytometry (p = 0.021). Longitudinal analysis revealed proliferation of these cells in peripheral blood post-treatment. Shared TCR clonotypes were identified across blood and tumour samples. Pseudotime analysis indicated differentiation of these cells into exhausted and cytotoxic NK-like CD8 + T cells upon tumour infiltration.

Conclusion

These findings suggest that CD8 + CX3CR1 + T cells may represent circulating cytotoxic precursors associated with effective NA-ICB responses, suggesting their potential as predictive biomarkers and therapeutic targets for adoptive cell therapy.