Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma

Abstract Tertiary lymphoid structures (TLSs) are considered to have a good prognosis in multiple solid tumors. However, the prognostic value of TLS in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we retrospectively enrolled 185 ESCC patients who underwent surgical resection....

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Main Authors: Rutao Li, Xing Huang, Wenmin Yang, Jifan Wang, Yingkuan Liang, Te Zhang, Qixing Mao, Wenjie Xia, Lin Xu, Xinyu Xu, Gaochao Dong, Feng Jiang
Format: Article
Language:English
Published: Wiley 2022-09-01
Series:The Journal of Pathology: Clinical Research
Subjects:
Online Access:https://doi.org/10.1002/cjp2.281
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author Rutao Li
Xing Huang
Wenmin Yang
Jifan Wang
Yingkuan Liang
Te Zhang
Qixing Mao
Wenjie Xia
Lin Xu
Xinyu Xu
Gaochao Dong
Feng Jiang
author_facet Rutao Li
Xing Huang
Wenmin Yang
Jifan Wang
Yingkuan Liang
Te Zhang
Qixing Mao
Wenjie Xia
Lin Xu
Xinyu Xu
Gaochao Dong
Feng Jiang
author_sort Rutao Li
collection DOAJ
description Abstract Tertiary lymphoid structures (TLSs) are considered to have a good prognosis in multiple solid tumors. However, the prognostic value of TLS in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we retrospectively enrolled 185 ESCC patients who underwent surgical resection. Hematoxylin and eosin staining was performed to investigate the presence, the abundance, the maturation, and the location of TLSs. We explored the cellular composition of TLSs using traditional immunohistochemistry in serial sections. The prognostic value of TLSs was investigated by univariate and multivariate analyses. A nomogram was constructed to predict the prognosis. TLS‐positive tumors were infiltrated with more CD45+ leukocytes, CD20+ B cells, CD4+ and CD8+ T cells, and CD11c+ dendritic cells(DCs) compared with negative tumors. Kaplan–Meier curves showed that the presence and the abundance of TLSs were associated with longer disease‐free survival (DFS) (p = 0.0130) and overall survival (OS) (p = 0.0164). In addition, patients with tumors containing more CD20+ B cell infiltration had longer DFS (p = 0.0105) and OS (p = 0.0341). Multivariate analyses demonstrated that the presence of TLSs was an independent prognostic factor for DFS (hazard ratio [HR] = 0.384, p < 0.001) and OS (HR = 0.293, p < 0.001). The nomogram that integrated the tumor stage, histologic grade, and TLS presence had higher prognostic accuracy. Our study suggests that ESCC‐related TLSs can be used as a new biomarker for the prognosis of ESCC patients, and further understanding of their formation and mechanism of induction can provide a possible direction and target for immunotherapy of ESCC.
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spelling doaj.art-ff7c94970ee04c01ac74937e260d2a562022-12-22T00:54:30ZengWileyThe Journal of Pathology: Clinical Research2056-45382022-09-018542243510.1002/cjp2.281Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinomaRutao Li0Xing Huang1Wenmin Yang2Jifan Wang3Yingkuan Liang4Te Zhang5Qixing Mao6Wenjie Xia7Lin Xu8Xinyu Xu9Gaochao Dong10Feng Jiang11Department of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing PR ChinaDepartment of Pathology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research The Affiliated Cancer Hospital of Nanjing Medical University Nanjing PR ChinaDepartment of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing PR ChinaDepartment of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing PR ChinaDepartment of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing PR ChinaDepartment of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing PR ChinaDepartment of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing PR ChinaDepartment of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing PR ChinaDepartment of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing PR ChinaDepartment of Pathology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research The Affiliated Cancer Hospital of Nanjing Medical University Nanjing PR ChinaDepartment of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing PR ChinaDepartment of Thoracic Surgery Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research Nanjing PR ChinaAbstract Tertiary lymphoid structures (TLSs) are considered to have a good prognosis in multiple solid tumors. However, the prognostic value of TLS in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we retrospectively enrolled 185 ESCC patients who underwent surgical resection. Hematoxylin and eosin staining was performed to investigate the presence, the abundance, the maturation, and the location of TLSs. We explored the cellular composition of TLSs using traditional immunohistochemistry in serial sections. The prognostic value of TLSs was investigated by univariate and multivariate analyses. A nomogram was constructed to predict the prognosis. TLS‐positive tumors were infiltrated with more CD45+ leukocytes, CD20+ B cells, CD4+ and CD8+ T cells, and CD11c+ dendritic cells(DCs) compared with negative tumors. Kaplan–Meier curves showed that the presence and the abundance of TLSs were associated with longer disease‐free survival (DFS) (p = 0.0130) and overall survival (OS) (p = 0.0164). In addition, patients with tumors containing more CD20+ B cell infiltration had longer DFS (p = 0.0105) and OS (p = 0.0341). Multivariate analyses demonstrated that the presence of TLSs was an independent prognostic factor for DFS (hazard ratio [HR] = 0.384, p < 0.001) and OS (HR = 0.293, p < 0.001). The nomogram that integrated the tumor stage, histologic grade, and TLS presence had higher prognostic accuracy. Our study suggests that ESCC‐related TLSs can be used as a new biomarker for the prognosis of ESCC patients, and further understanding of their formation and mechanism of induction can provide a possible direction and target for immunotherapy of ESCC.https://doi.org/10.1002/cjp2.281tertiary lymphoid structureesophageal squamous cell carcinomaprognostic valueimmunotherapy target
spellingShingle Rutao Li
Xing Huang
Wenmin Yang
Jifan Wang
Yingkuan Liang
Te Zhang
Qixing Mao
Wenjie Xia
Lin Xu
Xinyu Xu
Gaochao Dong
Feng Jiang
Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma
The Journal of Pathology: Clinical Research
tertiary lymphoid structure
esophageal squamous cell carcinoma
prognostic value
immunotherapy target
title Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma
title_full Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma
title_fullStr Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma
title_full_unstemmed Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma
title_short Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma
title_sort tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma
topic tertiary lymphoid structure
esophageal squamous cell carcinoma
prognostic value
immunotherapy target
url https://doi.org/10.1002/cjp2.281
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