Investigating the correlation between tertiary lymphoid structures and clinical outcomes in pancreatic ductal adenocarcinoma: insights into tumor immunology

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and high mortality rates, necessitating the identification of reliable biomarkers for patient stratification. This study investigates the prognostic significance and biological functions of tertiary lymphoid structures (TLS) i...

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Main Authors: Lingbo Hu, Yanhong Xiao, Ning Jiang, Yufen Hu, Liewang Qiu, Bo Geng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1569947/full
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author Lingbo Hu
Lingbo Hu
Lingbo Hu
Yanhong Xiao
Yanhong Xiao
Yanhong Xiao
Ning Jiang
Ning Jiang
Yufen Hu
Liewang Qiu
Bo Geng
author_facet Lingbo Hu
Lingbo Hu
Lingbo Hu
Yanhong Xiao
Yanhong Xiao
Yanhong Xiao
Ning Jiang
Ning Jiang
Yufen Hu
Liewang Qiu
Bo Geng
author_sort Lingbo Hu
collection DOAJ
description Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and high mortality rates, necessitating the identification of reliable biomarkers for patient stratification. This study investigates the prognostic significance and biological functions of tertiary lymphoid structures (TLS) in PDAC. We analyzed clinical data from 65 PDAC patients and RNA sequencing data from The Cancer Genome Atlas (TCGA) to evaluate the presence of TLS and its impact on overall survival (OS) and recurrence-free survival (RFS). Our results demonstrate that patients with intratumoral TLS (iTLS+) exhibit significantly improved OS and RFS compared to those without iTLS (iTLS-). Additionally, the presence of TLS correlates with enhanced immune cell infiltration, including increased levels of B cells, T cells, and plasma cells, suggesting a more active anti-tumor immune response in the TLS+ group. Furthermore, we found significant differences in gene expression between TLS+ and TLS- groups, particularly in pathways related to tumor proliferation and immune regulation. Notably, our findings indicate that the mutation frequency of key oncogenes, such as TP53, differs significantly between these groups, potentially influencing patient outcomes. This study underscores the potential of TLS as a prognostic biomarker in PDAC and highlights their role in modulating the tumor microenvironment. Our findings pave the way for further research into TLS-targeted therapeutic strategies aimed at improving the clinical management of pancreatic cancer.
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spelling doaj-art-e73f6719e6d245bd99316be3e1570fbc2025-08-20T02:24:14ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15699471569947Investigating the correlation between tertiary lymphoid structures and clinical outcomes in pancreatic ductal adenocarcinoma: insights into tumor immunologyLingbo Hu0Lingbo Hu1Lingbo Hu2Yanhong Xiao3Yanhong Xiao4Yanhong Xiao5Ning Jiang6Ning Jiang7Yufen Hu8Liewang Qiu9Bo Geng10Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, ChinaDepartment of Hepatopancreatobiliary Surgery, Enze Hospital, Taizhou Enze Medical Center, Taizhou, Zhejiang, ChinaDepartment of Pathology, Dianjiang County Hospital of Traditional Chinese Medicine, Chongqing, ChinaMolecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, ChinaDepartment of Pathology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaMolecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, ChinaDepartment of Pathology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of General Practice, Shiqiaopu Community Health Service Center, Chongqing, ChinaDepartment of Gastroenterology, Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Hepatobiliary Surgery, People’s Hospital of He Chuan Chong Qing, Chongqing, ChinaPancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and high mortality rates, necessitating the identification of reliable biomarkers for patient stratification. This study investigates the prognostic significance and biological functions of tertiary lymphoid structures (TLS) in PDAC. We analyzed clinical data from 65 PDAC patients and RNA sequencing data from The Cancer Genome Atlas (TCGA) to evaluate the presence of TLS and its impact on overall survival (OS) and recurrence-free survival (RFS). Our results demonstrate that patients with intratumoral TLS (iTLS+) exhibit significantly improved OS and RFS compared to those without iTLS (iTLS-). Additionally, the presence of TLS correlates with enhanced immune cell infiltration, including increased levels of B cells, T cells, and plasma cells, suggesting a more active anti-tumor immune response in the TLS+ group. Furthermore, we found significant differences in gene expression between TLS+ and TLS- groups, particularly in pathways related to tumor proliferation and immune regulation. Notably, our findings indicate that the mutation frequency of key oncogenes, such as TP53, differs significantly between these groups, potentially influencing patient outcomes. This study underscores the potential of TLS as a prognostic biomarker in PDAC and highlights their role in modulating the tumor microenvironment. Our findings pave the way for further research into TLS-targeted therapeutic strategies aimed at improving the clinical management of pancreatic cancer.https://www.frontiersin.org/articles/10.3389/fonc.2025.1569947/fulltertiary lymphoid structurespancreatic ductal adenocarcinomaimmune regulationprognostic biomarkeroverall survival
spellingShingle Lingbo Hu
Lingbo Hu
Lingbo Hu
Yanhong Xiao
Yanhong Xiao
Yanhong Xiao
Ning Jiang
Ning Jiang
Yufen Hu
Liewang Qiu
Bo Geng
Investigating the correlation between tertiary lymphoid structures and clinical outcomes in pancreatic ductal adenocarcinoma: insights into tumor immunology
Frontiers in Oncology
tertiary lymphoid structures
pancreatic ductal adenocarcinoma
immune regulation
prognostic biomarker
overall survival
title Investigating the correlation between tertiary lymphoid structures and clinical outcomes in pancreatic ductal adenocarcinoma: insights into tumor immunology
title_full Investigating the correlation between tertiary lymphoid structures and clinical outcomes in pancreatic ductal adenocarcinoma: insights into tumor immunology
title_fullStr Investigating the correlation between tertiary lymphoid structures and clinical outcomes in pancreatic ductal adenocarcinoma: insights into tumor immunology
title_full_unstemmed Investigating the correlation between tertiary lymphoid structures and clinical outcomes in pancreatic ductal adenocarcinoma: insights into tumor immunology
title_short Investigating the correlation between tertiary lymphoid structures and clinical outcomes in pancreatic ductal adenocarcinoma: insights into tumor immunology
title_sort investigating the correlation between tertiary lymphoid structures and clinical outcomes in pancreatic ductal adenocarcinoma insights into tumor immunology
topic tertiary lymphoid structures
pancreatic ductal adenocarcinoma
immune regulation
prognostic biomarker
overall survival
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1569947/full
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