Abstract 2211: The prognostic role of tertiary lymphoid structure (TLS) in locally advanced esophageal squamous cell carcinoma (ESCC)
Authors: Huang Ta-Chen , Liang Cher-Wei , Li Yu-I , Guo Jhe-Cyuan , Lin Chia-Chi , Lee Jang-Ming , Chao Yin-Kai , Hsu Chih-Hung 
Published: June 2023

Abstract
Introduction: The presence of TLS in tumors is associated with improved efficacy of immunotherapy in various types of cancer. The significance of TLS in patients with ESCC has been sporadically reported. The study aimed to investigate the prognostic significance of TLS in patients with locally advanced ESCC receiving neoadjuvant chemoradiotherapy (CRT).
Patients and Methods: We included two cohorts of locally advanced ESCC patients from two referral centers of Taiwan. Cohort A consisted of 99 patients treated with paclitaxel/cisplatin-based CRT, 69 of them being neoadjuvant CRT and 30 of them being definitive CRT, between 2002 and 2015; cohort B consisted of 67 patients treated with paclitaxel/carboplatin-based neoadjuvant CRT between 2012 and 2018. Primary tumor tissues were retrospectively collected for immunohistochemical stains by CD20 (clone L26; Zytomed, Berlin, Germany) and CD23 (clone DAK-CD23; agilent Dako, California, U.S.A.). TLS was defined as aggregation of CD20 B cells, and mature TLS was defined as TLS with CD23-positively stained germinal center. Patients’ characteristics were compared between those with or without TLS or mature TLS. The impact of TLS or mature TLS on patients’ overall survival (OS) was analyzed by Kaplan-Meier method and log rank test.
Results: In cohort A (median age of 56 years, M:F= 88:11), no TLS, immature TLS, and mature TLS were seen in 52, 35, and 12 patients, respectively. In cohort B (median age of 55 years, M:F= 64:3), no TLS, immature TLS, and mature TLS were seen in 27, 25, and 15, respectively. In cohort A, the presence of TLS is more commonly seen in ESCC with the primary site at upper (58%) and lower segments (63%) than middle segment of esophagus (35%) (p=0.039), and the mature TLS is more commonly seen at lower segment (25%) than other segments (8%) (p=0.033). The pathological complete response (pCR) was not significant different between patients with vs without TLS in cohort A (39% vs 43 %, p= 0.75), but trended to be lower in patients with TLS than without in cohort B (28% vs 52 %, p= 0.061). Besides, pCR rate trended to be lower in patients with mature TLS than without in both cohorts (13% vs 45 %, p= 0.080, for cohort A; 28% vs 43 %, p= 0.23, for cohort B). As patients with or without TLS did not differ in their OS in both cohorts, patients with mature TLS trended to have worse overall survival in both cohort A (HR: 1.4 [95% CI 0.33-3.05], p=0.29) and cohort B (HR: 1.6 [95% CI 0.81-2.98], p=0.15).
Conclusion: In two independent cohorts of locally advanced ESCC patients receiving paclitaxel/platinum-based CRT, we did not find the correlation of the presence of TLS or mature TLS in pre-treatment primary ESCC tumor tissue with the favorable treatment outcomes. (The study was supported by the grant NTUH 110-S5021, the grant MOST 108-2314-B-002-076-MY3, and grant 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. The prognostic role of tertiary lymphoid structure (TLS) in locally advanced esophageal squamous cell carcinoma (ESCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2211.