This study first systematically demonstrates that CD8+ nTIL density in necrotic tumor regions strongly correlates with event-free survival (EFS) in NSCLC patients following neoadjuvant PD-1 blockade combined with chemotherapy. The research indicates that CD8+ nTIL density surpasses traditional radiological and pathological response assessments in prognostic prediction, exhibiting independent prognostic value and offering a more precise biomarker for guiding treatment decisions.
Literature Overview
The article 'CD8+ TILs in necrotic tumors after neoadjuvant immunochemotherapy predict outcomes in non-small-cell lung cancer patients' published in Signal Transduction and Targeted Therapy reviews predictive factors for therapeutic response in NSCLC patients undergoing neoadjuvant PD-1 blockade combined with chemotherapy. The study identifies significant associations between CD8+ tumor-infiltrating lymphocyte (nTIL) density in necrotic regions and patient prognosis, independent of PD-L1 expression or lymph node metastasis status, suggesting its potential as an independent prognostic biomarker.
Background Knowledge
Non-small-cell lung cancer (NSCLC) represents the most common lung cancer subtype, with surgery remaining the primary treatment option for early-stage patients despite high postoperative recurrence rates. Recent years have seen promising pathological response rates from neoadjuvant immunotherapy combined with chemotherapy, particularly in achieving major pathological response (MPR) and complete pathological response (pCR). However, MPR and pCR alone cannot effectively stratify patient prognosis, as some MPR patients still experience early recurrence, necessitating more accurate biomarkers for efficacy evaluation. Tumor necrosis, a common histopathological phenomenon typically associated with tumor aggressiveness, may retain T-cell-specific antigens post-immunotherapy, enabling immunohistochemical (IHC) detection of tumor-infiltrating lymphocytes (TILs), particularly CD8+ T cells. These nTILs may reflect the immune system's tumor-clearing capacity, serving as a novel predictor for therapeutic response. This study aims to evaluate the prognostic value of CD8+ nTIL density in NSCLC neoadjuvant treatment and compare its predictive performance against traditional radiological and pathological responses.
Research Methods and Experiments
This retrospective analysis included 200 NSCLC patients who received neoadjuvant PD-1 blockade combined with chemotherapy, with 99 cases containing necrotic tumor regions suitable for nTIL density assessment. All samples were collected from three medical centers, utilizing immunohistochemistry (IHC) to measure CD3 and CD8+ TIL density, followed by statistical analysis integrating clinical follow-up data. The research team evaluated relationships between event-free survival (EFS) and nTIL density using Kaplan-Meier analysis and univariate Cox proportional hazards models, while receiver operating characteristic (ROC) curves were employed to assess predictive performance.
Key Conclusions and Perspectives
Research Significance and Prospects
This study establishes the first systematic evaluation of CD8+ nTIL density as a prognostic biomarker for NSCLC patients after neoadjuvant immunochemotherapy, highlighting its potential for clinical decision-making. Future research should validate this marker's stability in larger cohorts and explore its applicability across other solid tumors. Development of standardized nTIL assessment tools, such as machine learning-based software, could enhance clinical implementation efficiency. These findings provide a novel biomarker for therapeutic response evaluation in neoadjuvant immunochemotherapy and may inform postoperative adjuvant treatment strategies.
Conclusion
This study identifies CD8+ nTIL density in necrotic regions as a robust predictor of event-free survival (EFS) for NSCLC patients following neoadjuvant immunochemotherapy. Compared to traditional radiological and pathological response assessments, CD8+ nTIL density demonstrates superior predictive accuracy and stability, independent of PD-L1 expression or lymph node metastasis status. The research emphasizes the association between immune activity in necrotic regions and long-term patient prognosis, offering a novel biomarker for personalized NSCLC treatment evaluation. These findings not only advance optimization of neoadjuvant immunotherapy response evaluation systems but also provide theoretical foundations for future clinical trial designs.
