Abstract
This retrospective study analyzed 73 patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoimmunotherapy, aiming to investigate the impact of the multiple heterogeneity of tertiary lymphoid structures (TLS) on treatment efficacy and prognosis. The results demonstrated that intratumoral TLS presence correlated with superior radiological and pathological responses, whereas peritumoral TLS expression was associated with poorer outcomes. Regarding spatial heterogeneity, the subgroup characterized by high intratumoral TLS abundance combined with absent peritumoral TLS exhibited the most favorable progression-free survival (PFS) and overall survival (OS). Furthermore, a higher degree of TLS maturation was significantly associated with improved survival benefits. Multivariate analysis confirmed that body mass index (BMI) served as an independent protective factor for both PFS and OS, while pre-treatment TNM stage emerged as an independent risk factor for PFS. These findings suggest that TLS holds promise as a potential predictive biomarker for the efficacy of neoadjuvant chemoimmunotherapy.