What question did this study set out to answer?

This study aims to evaluate the predictive value of tertiary lymphoid structures (TLS) on neoadjuvant chemoradiotherapy outcomes in esophageal squamous cell carcinoma.

June 3, 2026Open Access

Tertiary lymphoid structures predict outcomes of neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma

Key Points

This study aims to evaluate the predictive value of tertiary lymphoid structures (TLS) on neoadjuvant chemoradiotherapy outcomes in esophageal squamous cell carcinoma.
Retrospective enrollment of 137 patients with locally advanced ESCC from two referral centers.
Patients received paclitaxel/platinum-based neoadjuvant chemoradiotherapy before esophagectomy.
TLS status was assessed through immunohistochemical staining for CD20 and CD23, and outcomes were analyzed using logistic regression and Kaplan-Meier methods.
The pathologic complete response rate was lower in the mature TLS group compared to the no TLS group (24% vs 47%, P=0.028).
Multivariate analysis indicated mature TLS as an independent predictor of non-complete response (OR: 3.8; P=0.023) and poor overall survival (HR: 3.0; P=0.0008).
PD-L1 TC was a predictor of poor overall survival (HR: 1.57; P=0.047) while PD-L1 IC was associated with better overall survival (HR: 0.31; P<0.0001).

Abstract

Tertiary lymphoid structure (TLS) is associated with improved survival across cancers. This study was conducted to investigate the efficacy of TLSs in predicting the outcomes of neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC). We retrospectively enrolled patients with locally advanced ESCC from 2 referral centers in Taiwan. All patients received paclitaxel/platinum-based neoadjuvant chemoradiotherapy before undergoing esophagectomy. Primary tumor tissues were subjected to immunohistochemical staining to assess CD20 and CD23 expression. TLSs were defined as aggregates of CD20-positive B cells, and mature TLSs were defined as TLSs with CD23-positive germinal centers. The patients were stratified by TLS status into no, immature, and mature TLS groups. The effects of mature TLSs on treatment outcomes were analyzed through logistic regression for pathologic complete response (pCR) and through Kaplan–Meier analysis, log-rank tests, and Cox regression for overall survival (OS). PD-L1 expression on immune cells (PD-L1 IC) and tumor cells (PD-L1 TC) were included in the multivariate analysis. One hundred and thirty-seven patients were enrolled. The no, immature, and mature TLS groups comprised 64, 40, and 33 patients, respectively. The pCR rate was lower in the mature than in the no TLS (24% vs 47%, P = .028). A trend toward poor OS was observed in the mature (HR: 1.4; P = .15) compared with the no TLS. Multivariate analysis indicated mature TLS as an independent predictor of non-pCR (OR: 3.8; P = .023) and poor OS (HR: 3.0; P = .0008), PD-L1 TC as an independent predictor of poor OS (HR: 1.57, P = 0.047), and PD-L1 IC as an independent predictor of good OS (HR: 0.31, P < 0.0001). Mature TLS and PD-L1 TC are independent predictors of poor treatment outcomes, and PD-L1 IC is an independent predictor of good treatment outcomes, in patients with locally advanced ESCC receiving neoadjuvant chemoradiotherapy.

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Cite This Study

Huang et al. (Mon,) studied this question.

synapsesocial.com/papers/6a1fc616dee9eb8c0dce757c https://doi.org/https://doi.org/10.1186/s12885-026-16163-3

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