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探究三级淋巴结构与胰腺导管腺癌临床结局之间的相关性:肿瘤免疫学见解

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

作者信息

Hu Lingbo, Xiao Yanhong, Jiang Ning, Hu Yufen, Qiu Liewang, Geng Bo

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China.

出版信息

Front Oncol. 2025 Jun 26;15:1569947. doi: 10.3389/fonc.2025.1569947. eCollection 2025.

DOI:10.3389/fonc.2025.1569947
PMID:40641930
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12240791/
Abstract

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.

摘要

胰腺导管腺癌(PDAC)预后较差且死亡率高,因此需要识别可靠的生物标志物用于患者分层。本研究调查了胰腺导管腺癌中三级淋巴结构(TLS)的预后意义和生物学功能。我们分析了65例胰腺导管腺癌患者的临床数据以及来自癌症基因组图谱(TCGA)的RNA测序数据,以评估TLS的存在及其对总生存期(OS)和无复发生存期(RFS)的影响。我们的结果表明,与无瘤内TLS(iTLS-)的患者相比,有瘤内TLS(iTLS+)的患者的OS和RFS显著改善。此外,TLS的存在与免疫细胞浸润增强相关,包括B细胞、T细胞和浆细胞水平升高,这表明TLS+组的抗肿瘤免疫反应更为活跃。此外,我们发现TLS+组和TLS-组之间基因表达存在显著差异,特别是在与肿瘤增殖和免疫调节相关的通路中。值得注意的是,我们的研究结果表明,关键癌基因如TP53的突变频率在这些组之间存在显著差异,这可能影响患者的预后。本研究强调了TLS作为胰腺导管腺癌预后生物标志物的潜力,并突出了它们在调节肿瘤微环境中的作用。我们的研究结果为进一步研究以TLS为靶点的治疗策略铺平了道路,旨在改善胰腺癌的临床管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26fb/12240791/5f869933599b/fonc-15-1569947-g008.jpg
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本文引用的文献

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J Transl Med. 2025 Mar 10;23(1):301. doi: 10.1186/s12967-025-06152-8.
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Overcoming therapy resistance in pancreatic cancer: New insights and future directions.克服胰腺癌的治疗抵抗:新的见解和未来方向。
Biochem Pharmacol. 2024 Nov;229:116492. doi: 10.1016/j.bcp.2024.116492. Epub 2024 Aug 15.
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Prognostic value of tertiary lymphoid structures in hepatocellular carcinoma: a meta-analysis and systematic review.
三级淋巴结构在肝细胞癌中的预后价值:荟萃分析和系统评价。
Front Immunol. 2024 Jun 3;15:1390938. doi: 10.3389/fimmu.2024.1390938. eCollection 2024.
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Integrating tertiary lymphoid structure-associated genes into computational models to evaluate prognostication and immune infiltration in pancreatic cancer.将三级淋巴结构相关基因纳入计算模型,以评估胰腺癌的预后和免疫浸润。
J Leukoc Biol. 2024 Sep 2;116(3):589-600. doi: 10.1093/jleuko/qiae067.
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Spatial relationship of tertiary lymphoid structures and tumor-associated neutrophils in bladder cancer and prognostic potential for anti-PD-L1 immunotherapy.膀胱癌中三级淋巴结构与肿瘤相关中性粒细胞的空间关系及抗PD-L1免疫治疗的预后潜力
Cancer Commun (Lond). 2024 Apr;44(4):499-503. doi: 10.1002/cac2.12491. Epub 2023 Oct 20.
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J Immunother Cancer. 2023 Jun;11(6). doi: 10.1136/jitc-2023-006698.
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