Cancer lettersAug 14, 2024

Tertiary lymphoid structures linked to better survival and their locations in esophageal squamous cell cancer after pre-surgery treatments

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 6, 2026

Abstract

TLSs were observed in 359 esophageal squamous cell carcinoma patients receiving various neoadjuvant therapies.

Mature TLS (MTLS) was identified as an independent prognostic factor in esophageal squamous cell carcinoma.
The neoadjuvant immunotherapy group had the lowest cases of immature TLS, while the neoadjuvant chemoradiotherapy group had the lowest MTLSs.
MTLSs were primarily found in stromal and normal compartments and were positively correlated with the outcomes of neoadjuvant therapy.
The neoadjuvant immunotherapy group exhibited the highest density of T cells within 150 μm of TLSs compared to other groups.
B cells were concentrated within TLSs, while T cells were mostly dispersed beyond 150 μm from TLSs.
The novel PD-L1 combined positive score was positively associated with MTLSs and the efficacy of neoadjuvant therapies.

Simplified

Tertiary lymphoid structures (TLSs) were associated with survival in esophageal squamous cell carcinoma (ESCC) undergoing surgery alone (SA). However, their clinical relevance in neoadjuvant therapies remains less known. Here, we firstly investigated the presence, maturation and spatial distribution of TLSs in 359 ESCC patients receiving neoadjuvant chemotherapy (NCT), neoadjuvant immunotherapy (NCI), neoadjuvant chemoradiotherapy (NCRT) or SA. We found mature TLS (MTLS) was an independent prognostic factor in ESCC. NCI group had the lowest immature TLS cases. NCRT group had the lowest MTLSs. MTLSs mostly located in stromal and normal compartments; these MTLSs were positively correlated with neoadjuvant therapy outcomes. NCI group displayed the highest T cells within 150 μm proximity of TLSs among the four groups. Most T cells were dispersed up to more than 150 μm from TLSs, while B cells remained concentrated within TLSs. Innate lymphoid cells and follicular dendritic cells infiltrated and connected with survival differently in NCRT and NCI groups compared with SA group. The novel PD-L1 combined positive score, NCPS, was positively connected with MTLSs and neoadjuvant therapy efficacy. ScRNA-seq analysis revealed TLS+ tumors had increased plasma cells, B cells, Th17, Tfh and Th1, and elevated exhausted CD8T cells that highly expressed checkpoint molecules and granzymes. Conclusively, MTLSs favored treatment outcome in ESCC patients receiving multiple neoadjuvant therapies. The spatial distribution of MTLSs was associated with multiregional immune status modified by the neoadjuvant therapies. +

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Tertiary lymphoid structures linked to better survival and their locations in esophageal squamous cell cancer after pre-surgery treatments

Abstract

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