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<p>Neoadjuvant immunochemotherapy has shown promising results, with major pathologic response (MPR, ≤10% residual viable tumors [RVT]) as the primary outcome. However, %RVT showed limited predictive power in stratifying outcomes within the MPR and non-MPR groups. To identify a better prognostic marker, this study analyzed 200 non-small-cell lung cancer (NSCLC) samples after neoadjuvant PD-1 blockade combined with chemotherapy across three medical centers. Among these patients, 99 had necrotic regions in their residual lesions. We found that tumor-infiltrating lymphocytes in necrotic areas (nTILs) lose their cellular structure, but retained T-cell-specific antigens, making them detectable by immunohistochemistry. Regardless of PD-L1 status or lymph node metastasis, patients with high CD8<sup>+</sup> nTIL density had significantly improved event-free survival (EFS) (hazard ratio [HR]: 0.08; 95% CI: [0.01–0.62]; <i>p</i> = 0.0019). Furthermore, CD8<sup>+</sup> nTIL density improved prognostic predictions for patients within the MPR (<i>p</i> = 0.017) and non-MPR groups (<i>p</i> = 0.076). Radiological responses did not correlate with MPR, CD8<sup>+</sup> nTIL density or EFS. 41.5% MPR cases were misclassified by radiological assessments. When compared with radiographic response and pathological response, CD8<sup>+</sup> nTIL density outperformed these traditional parameters in approximating EFS. These findings demonstrate that the CD8<sup>+</sup> nTIL density is a robust predictor of EFS in NSCLC patients treated with neoadjuvant immunochemotherapy and has great potential in guiding treatment decisions.</p>

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CD8+ TILs in necrotic tumors after neoadjuvant immunochemotherapy predict outcomes in non-small-cell lung cancer patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月9日

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  • Haifeng Lin,
  • Yi Han,
  • Lei Guo,
  • Caigang Liu,
  • Hefei Li,
  • Jie Li,
  • Chong Wang,
  • Lijuan Zhou,
  • Xiangna Zhang,
  • Lisha Sun,
  • Ying Yi Zhang,
  • Xiaojing Chu,
  • Jianquan Shi,
  • Xiaoqing Cao,
  • Yifang Chen,
  • Zhiqing Qin,
  • Jiaming Bao,
  • Shiya Wan,
  • Hao Chen,
  • Xiaoran Tang,
  • Xiang Li,
  • Xinyu Wang,
  • Yuting Cheng,
  • Yixia Li,
  • Jie Zhang,
  • Chang Liu,
  • Xuguang Zhang,
  • Yanan Wang,
  • Yi Hu,
  • Nanying Che,
  • Xiaowei Xu,
  • Hezhe Lu

摘要

Neoadjuvant immunochemotherapy has shown promising results, with major pathologic response (MPR, ≤10% residual viable tumors [RVT]) as the primary outcome. However, %RVT showed limited predictive power in stratifying outcomes within the MPR and non-MPR groups. To identify a better prognostic marker, this study analyzed 200 non-small-cell lung cancer (NSCLC) samples after neoadjuvant PD-1 blockade combined with chemotherapy across three medical centers. Among these patients, 99 had necrotic regions in their residual lesions. We found that tumor-infiltrating lymphocytes in necrotic areas (nTILs) lose their cellular structure, but retained T-cell-specific antigens, making them detectable by immunohistochemistry. Regardless of PD-L1 status or lymph node metastasis, patients with high CD8+ nTIL density had significantly improved event-free survival (EFS) (hazard ratio [HR]: 0.08; 95% CI: [0.01–0.62]; p = 0.0019). Furthermore, CD8+ nTIL density improved prognostic predictions for patients within the MPR (p = 0.017) and non-MPR groups (p = 0.076). Radiological responses did not correlate with MPR, CD8+ nTIL density or EFS. 41.5% MPR cases were misclassified by radiological assessments. When compared with radiographic response and pathological response, CD8+ nTIL density outperformed these traditional parameters in approximating EFS. These findings demonstrate that the CD8+ nTIL density is a robust predictor of EFS in NSCLC patients treated with neoadjuvant immunochemotherapy and has great potential in guiding treatment decisions.