Prognostic and clinicopathological significance of tertiary lymphoid structure in esophageal squamous cell carcinoma: a systematic review and meta-analysis review.

Abstract

Tertiary lymphoid structures (TLS), ectopic immune cell aggregates in non-lymphoid tissues, have emerged as potential predictors of esophageal squamous cell carcinoma (ESCC) outcomes. Given increasing evidence, we conducted an updated meta-analysis to systematically evaluate their prognostic and clinicopathological significance. A comprehensive literature search was performed through PubMed, Embase, Web of Science, Scopus, and Cochrane Library (up to June 2024) for studies assessing TLS associations with TNM staging and survival outcomes (OS/PFS) in ESCC. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. This meta-analysis incorporated seven studies comprising nine separate datasets that evaluated the impact of TLS in ESCC. The pooled analysis demonstrated a significant positive correlation between TLS presence and more advanced T stage (OR = 2.65, 95%CI: 1.86-3.78; p < 0.01) but not N stage (OR = 1.27, 95%CI: 0.85-1.89; p = 0.24). Additionally, TLS presence was significantly associated with enhanced overall survival (HR = 0.49, 95%CI: 0.41-0.58, p < 0.01) as well as progression-free survival (HR = 0.56, 95%CI: 0.45-0.69, p < 0.01). Notably, when assessed using combined HE and IHC criteria, the prognostic benefit of TLS was more pronounced, with HRs further decreasing to 0.40 (95% CI: 0.31-0.51) for OS and 0.50 (95% CI: 0.41-0.60) for PFS. These findings confirm that the presence of TLS, particularly when verified through combined HE staining and IHC, is an independent favorable prognostic factor in ESCC patients.