Abstract 7654: Tertiary lymphoid structure associates with poor prognosis in locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy

Abstract Introduction: Tertiary lymphoid structure (TLS) has been found to associate with good prognosis in various cancer types including esophageal squamous cell carcinoma (ESCC). A recent study involving patients receiving curative surgical resection alone for localized ESCC showed TLS as a favorable prognostic factor associated with improved progression free survival (Hayashi et al. British Journal of Cancer, 2023;128:2175-2185). Our study aimed to investigate the prognostic significance of TLS in patients with locally advanced ESCC receiving neoadjuvant chemoradiotherapy (CRT). Patients and Methods: We retrospectively enrolled 137 patients of locally advanced ESCC patients from two referral centers of Taiwan from 2002 to 2018. All patients received paclitaxel/platinum-based CRT followed by esophagectomy. Primary esophageal tumor tissues biopsied endoscopically before treatment were collected for immunohistochemical stains for CD20 (clone L26; Zytomed, Berlin, Germany) and CD23 (clone DAK-CD23; agilent Dako, California, U.S.A.). The TLS status of each patient was defined as no TLS (no aggregation of CD20-positive cells), immature TLS (aggregation of CD20-positive cells without CD23-positive cells in it), and mature TLS (aggregation of CD20-positive cells with CD23-positive cells in it). The associations of the TLS status with pathologic complete response (pCR) and overall survival (OS) were analyzed univariately and multivariately by logistic regression and cox regression, respectively. The variables included in the analyses were age, gender, tumor location, clinical T stage, clinical N stage, the institutes, PD-L1 expression on tumor cells (PD-L1 TC) and immune cells (PD-L1 IC), and the TLS status. Results: The median age was 54 years with 125 males and 12 females. The TLS status of no, immature, and mature TLS were seen in 64, 40, and 33 patients, respectively. Mature TLS was associated with PD-L1 IC (p=0.0007). Compared to no TLS, mature TLS associated with lower pCR rate (24% vs 47%) in both univariate (OR: 0.36, p=0.034) and multivariate (OR: 0.26, p=0.023) analysis. Compared to no TLS, mature TLS was associated with shorter OS (median OS: 27 vs 46 months) in multivariate analysis (HR: 2.96, p=0.0008), but not in univariate analysis (HR: 1.29, p=0.29). Other prognostic factors associated with OS in multivariate analysis include male gender (HR: 2.88, p=0.021), PD-L1 TC (HR: 1.62, p=0.039), and PD-L1 IC (HR: 0.30, p<0.0001). Conclusion: Mature TLS is an independent factor for poor treatment outcomes, including pathologic response and overall survival in locally advanced ESCC patients receiving neoadjuvant CRT. Additional studies are warranted to validate this finding. (The study was supported by the grant NTUH 110-S5021, MOST 108-2314-B-002-076-MY3, and MOHW 111-TDU-B-221-114006) Citation Format: Ta-Chen Huang, Cher-Wei Liang, Yu-I Li, Jhe-Cyuan Guo, Chia-Chi Lin, Jang-Ming Lee, Yin-Kai Chao, Chih-Hung Hsu. Tertiary lymphoid structure associates with poor prognosis in locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7654.