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 outcome...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.展开更多
基金H.L.is supported by the Institute of Zoology,Chinese Academy of Sciences,by grant funding from the National Natural Science Foundation of China(the National Science Fund for Excellent Young Scholars,E2111711 and General Program,E4110911)the Ministry of Science and Technology of the People’s Republic of China(National Key Basic Research Program,E310R811)+4 种基金the Chinese Academy of Sciences(Young Investigator Program in Basic Research,E2296111the Strategic Priority Research Program,XDC0200000the Incubation Fund Project from the Institute for Stem Cell and Regeneration,2023FH101,2023FH102,2023FH103)Y.H.is supported by grant funding from the Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(JYY2023-15)the Capability Enhancement Program(nlys2025-14).
文摘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.
