三级淋巴结构预测III期非小细胞肺癌的新辅助化学免疫治疗反应
Tertiary lymphoid structures predict the neoadjuvant chemoimmunotherapy response of stage III non-small cell lung cancer.
作者
作者单位
- Department of Oncology, Integrative Medical Center, Tianjin University/Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, China.
- Department of Oncology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, China.
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
摘要
中文
新辅助化学免疫治疗是可切除III期非小细胞肺癌（NSCLC）的标准治疗，但缺乏可靠的预测性生物标志物。三级淋巴结构（TLS）与NSCLC的生存相关，但它们在预测化学免疫治疗反应中的作用仍不清楚。本研究旨在全面表征TLS，并开发一个复合TLS评分来预测III期NSCLC的病理反应和生存。我们回顾性分析了接受新辅助化学免疫治疗的III期（IIIA-IIIC）NSCLC患者的肿瘤组织。使用苏木精-伊红（H&E）染色和多重免疫组织化学（mIHC）表征TLS的成熟度、密度、面积、位置和空间分布。开发了一个整合这些指标的复合TLS状态评分。分析了与病理反应、生存结局以及肿瘤微环境（TME）特征（包括程序性死亡配体1（PD-L1）表达和免疫细胞组成）的关联。更大的TLS成熟度与更早的T分期和临床分期相关。优越的TLS特征——包括高成熟度、高密度、大面积和间质位置——与改善的无进展生存期（PFS）显著相关。此外，获得主要病理反应（MPR）的患者表现出肿瘤具有更成熟和更致密的TLS，并伴随肿瘤浸润淋巴细胞的增加。有利的TLS状态（定义为复合评分=4）是优越PFS的稳健预测因子[曲线下面积（AUC）=0.82，P<0.001]。此外，TLS成熟度与TME中PD-L1表达呈负相关。TLS状态通过主动调节免疫TME的作用，可作为可切除III期NSCLC新辅助化学免疫治疗的预测性生物标志物。这可能为优化临床治疗提供有价值的进展。
English
Neoadjuvant chemoimmunotherapy is standard for resectable stage III non-small cell lung cancer (NSCLC), yet reliable predictive biomarkers are lacking. Tertiary lymphoid structures (TLS) correlate with survival in NSCLC, but their role in predicting chemoimmunotherapy response remains unclear. This study aimed to characterize TLS comprehensively and develop a composite TLS score to predict pathological response and survival in stage III NSCLC. We retrospectively analyzed tumor tissues from patients with stage III (IIIA-IIIC) NSCLC who underwent neoadjuvant chemoimmunotherapy. TLS were characterized using hematoxylin and eosin (H&E) staining and multiplex immunohistochemistry (mIHC) for maturity, density, area, location, and spatial distribution. A composite TLS status score integrating these metrics was developed. Associations with pathological response, survival outcomes, and features of the tumor microenvironment (TME), including programmed death-ligand 1 (PD-L1) expression and immune cell composition were analyzed. Greater TLS maturity was associated with earlier T-stage and clinical stages. Superior TLS characteristics-including advanced maturity, high density, large area, and stromal location-were significantly correlated with improved progression-free survival (PFS). Furthermore, patients who achieved a major pathological response (MPR) exhibited tumors characterized by more mature and denser TLS, and concomitant increase in tumor-infiltrating lymphocytes. A favorable TLS status, defined as a composite score =4, was a robust predictor of superior PFS [area under the curve (AUC) =0.82, P<0.001]. Furthermore, TLS maturity was inversely correlated with PD-L1 expression in the TME. TLS status, through its role in actively modulating the immune TME, serves as a predictive biomarker for neoadjuvant chemoimmunotherapy in resectable stage III NSCLC. This may offer a qualified advance for optimizing clinical therapeutics.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 3.4
- 新锐分区
- 3区