Background <p>Neoadjuvant chemo-immunotherapy improves outcomes in resectable non-small cell lung cancer (NSCLC), but predicting postoperative recurrence remains challenging. While the precursor exhausted T cell (Texp) index offers prognostic value, the broader tumor immune microenvironment (TIME) contains untapped predictive potential.</p> Methods <p>A secondary analysis was conducted based on single-cell RNA and TCR sequencing data from 138 NSCLC patients treated with neoadjuvant chemo-immunotherapy. Following collinearity filtering of 51 immune cell subtypes and the Texp index, LASSO-Cox regression was applied to develop a prognostic Risk Score for recurrence-free survival (RFS).</p> Results <p>A four-feature Risk Score was identified, incorporating the Texp index, CXCL13<sup>+</sup> Th1-like CD4<sup>+</sup> T cells, KLRB1<sup>+</sup> MAIT CD8<sup>+</sup> T cells, and terminally exhausted T cells. This score robustly stratified patients into distinct RFS groups and demonstrated independent prognostic value in multivariate analysis (HR = 6.090, <i>p =</i> 0.004). Compared to the baseline Texp index alone, the expanded Risk Score model yielded significantly improved predictive discrimination (mean ΔC-index = 0.096) and demonstrated superior net clinical benefit in decision curve analysis at 12 and 24 months.</p> Conclusion <p>This integrated single-cell immune Risk Score provides enhanced prognostic accuracy over single-metric biomarkers, offering a refined tool for postoperative risk stratification and personalized adjuvant management in NSCLC.</p>

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A single-cell derived immune risk score predicts recurrence in NSCLC following neoadjuvant chemo-immunotherapy

  • Jun Ge,
  • Xuesong Tong,
  • Xingxia Wang,
  • Jian Wang

摘要

Background

Neoadjuvant chemo-immunotherapy improves outcomes in resectable non-small cell lung cancer (NSCLC), but predicting postoperative recurrence remains challenging. While the precursor exhausted T cell (Texp) index offers prognostic value, the broader tumor immune microenvironment (TIME) contains untapped predictive potential.

Methods

A secondary analysis was conducted based on single-cell RNA and TCR sequencing data from 138 NSCLC patients treated with neoadjuvant chemo-immunotherapy. Following collinearity filtering of 51 immune cell subtypes and the Texp index, LASSO-Cox regression was applied to develop a prognostic Risk Score for recurrence-free survival (RFS).

Results

A four-feature Risk Score was identified, incorporating the Texp index, CXCL13+ Th1-like CD4+ T cells, KLRB1+ MAIT CD8+ T cells, and terminally exhausted T cells. This score robustly stratified patients into distinct RFS groups and demonstrated independent prognostic value in multivariate analysis (HR = 6.090, p = 0.004). Compared to the baseline Texp index alone, the expanded Risk Score model yielded significantly improved predictive discrimination (mean ΔC-index = 0.096) and demonstrated superior net clinical benefit in decision curve analysis at 12 and 24 months.

Conclusion

This integrated single-cell immune Risk Score provides enhanced prognostic accuracy over single-metric biomarkers, offering a refined tool for postoperative risk stratification and personalized adjuvant management in NSCLC.