ArticleFrontiers in immunology2025
Heterogeneity and distribution characteristics of tertiary lymphoid structures predict prognostic outcome in esophageal squamous cell carcinoma.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Review
- Prognostic value of tertiary lymphoid structures in high-risk esophageal squamous cell carcinoma following neoadjuvant chemoimmunotherapy.BMC cancer · 2026Article
- Digital Pathology and the AI-Based Quantification of the Tumor Microenvironment in Gastrointestinal Cancer: From Tumor Budding and Tumor-Infiltrating Lymphocytes to Tertiary Lymphoid Structures.International journal of molecular sciences · 2026Review
- Tertiary lymphoid structures in neoadjuvant and perioperative cancer immunotherapy: a review and proposed framework for biomarker interpretation and validation.Frontiers in immunology · 2026Review
- Terminally exhausted CD8Frontiers in immunology · 2025Review
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13 authors.
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Abstract
Objective: Tertiary Lymphoid Structures (TLSs) are ectopic lymphoid aggregates that form within the tumor microenvironment (TME) and are increasingly recognized as potential prognostic biomarkers in various cancers. However, the spatial heterogeneity and prognostic value of TLSs in esophageal squamous cell carcinoma (ESCC) remain poorly defined. This study aimed to characterize the spatial distribution patterns of TLSs and tumor-infiltrating lymphocytes (TILs), and to establish a refined prognostic model for ESCC patients in both surgery-only and neoadjuvant therapy cohorts. Methods: The TLSs were quantified through microscopic evaluation and digital slide analysis and correlated with prognosis by Cox regression and Kaplan-Meier analyses. The heterogeneity and clinical prognostic value of TLSs were explored by analyzing their distribution, density, and maximum diameter in different regions of ESCC patients. Results: TLSs showed spatial distribution heterogeneity in the tumor area, adjacent area, and marginal area, with consistent differences observed across different paraffin blocks. The distribution of iTIL and sTIL also exhibited certain spatial heterogeneity. In the surgical cohort (n = 117), the median Overall Survival (OS) and Disease-Free Survival (DFS) were 33 months and 15 months, respectively. Univariate analyses showed that TLS presence in tumor (TG), TLS-rich regions (TR), TLS ratio in normal regions (NR), tumor-stroma ratio (TSR), and both iTIL and sTIL levels were significantly associated with OS ( Conclusion: This study demonstrates that TLSs and TILs in ESCC are not only prognostically relevant but also spatially heterogeneous. The refined spatial immune profiling across multiple tumor regions improves prognostic stratification and may inform personalized treatment planning in ESCC.
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