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

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]; p = 0.0019). Furthermore, CD8<sup>+</sup> 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<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.

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Publication Details

Journal
Signal Transduction and Targeted Therapy
Published
2025-10-08
DOI
https://doi.org/10.1038/s41392-025-02435-0
Citations
3
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
3.14

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article

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

Lisha Sun, Haifeng Lin, Nanying Che, Shiya Wan et al.
3 citations
Signal Transduction and Targeted Therapy
Cancer Immunotherapy and Biomarkers
3.14
article

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

Lisha Sun, Haifeng Lin, Nanying Che, Shiya Wan, Hao Chen, Hezhe Lu, Jianquan Shi, Yi Hu, Xiaojing Chu, Jiaming Bao, Xiangna Zhang, Caigang Liu, Zhihai Qin, Y. Li, Lijuan Zhou, Lei Guo, Chong Wang, Xinyu Wang, Yanan Wang, Xiang Li, Jie Zhang, Chang Liu, Yifang Chen, Xiaoqing Cao, Yi Han, Hefei Li, Jie Li, Xiaowei Xu, Yu‐Ting Cheng, Xueying Tang, Ying Yi Zhang, Xuguang Zhang
article en
3 citations

Abstract

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]; p = 0.0019). Furthermore, CD8<sup>+</sup> 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<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.

Signal Transduction and Targeted TherapyVol. 10(1)
University of Science and Technology of China (CN), Capital Medical University (CN), Chinese Academy of Sciences (CN), Beijing Normal University (CN), Chinese PLA General Hospital (CN), Institute for Stem Cell Biology and Regenerative Medicine (IN), Beijing Chest Hospital (CN), Affiliated Hospital of Hebei University (CN), Institute of Zoology (CN), State Key Laboratory of Earth Surface Processes and Resource Ecology, University of Pennsylvania (US), Nanjing University (CN), South China University of Technology (CN), China Medical University (CN)
National Natural Science Foundation of China, Chinese Academy of Sciences, Ministry of Science and Technology of the People's Republic of China, National Outstanding Youth Science Fund Project of National Natural Science Foundation of China, Institute of Zoology, Chinese Academy of Sciences
Openalex Percentile: Top 7%
Cancer Immunotherapy and Biomarkers
3.14
DOIOpen Access PDFOpenAlex
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