Density and maturity ratio of tertiary lymphoid structures in stage II-III non-small cell lung cancer predict
Yi-Ming Liu1,2, Kai Zhao1,3, Mei Xie4
1Postgraduate School, Medical School of Chinese PLA, Beijing, China.
Background:
Tertiary lymphoid structure (TLS) has been proposed to assess the prognosis of patients with cancer. Due to the heterogeneity of the tumor microenvironment, TLS varies significantly in tumor tissues of different patients. This study aims to explore TLS in tumor tissues from patients with stage II-III non-small cell lung cancer (NSCLC) and their impact on postoperative recurrence risk.
Methods:
A total of 118 patients who underwent curative surgery for pathologically confirmed primary stage II-III NSCLC were included in this study. The density of TLS in tumor tissue was assessed using hematoxylin and eosin (HE) stained sections. Multiplex immunofluorescence was employed to evaluate the maturity of TLS by labeling follicular dendritic cells (FDC) and germinal centers (GC). Grouping was based on density to maturity ratios and overall survival (OS) and recurrence-free survival (RFS) differences were compared between subgroups.
Results:
Both TLS density score (D score) and maturity score (M score) were significantly associated with 3- and 5-year prognosis and were identified as independent predictors of postoperative 5-year recurrence risk [D score: hazard ratio (HR) 0.344, 95% confidence interval (CI): 0.157-0.756; M score: HR 0.148, 95% CI: 0.031-0.695]. An immune scoring system that combines D and M scores categorized stage II-III NSCLC patients into three immune classes with distinct prognoses (P=0.02). Higher immune scores correlated with lower postoperative recurrence risk.
Conclusions:
The density and maturity ratio of TLS are significantly associated with RFS in patients with stage II-III NSCLC, and the density score correlates significantly with OS. A novel immune classification system is proposed for predicting postoperative recurrence risk.
