Density of tertiary lymphoid structures and their correlation with prognosis in non-small cell lung cancer

Sep 22, 2026

Density and maturation of tertiary lymphoid structures (TLS) are examined as components of the tumor immune microenvironment in non-small cell lung cancer (NSCLC). Using immunohistochemistry on tumor tissue from 82 patients, TLS in intra-tumoral, invasive margin, and peritumoral regions are classified into early/primary (E-TLS) and secondary/follicular (F-TLS). E-TLS density in the invasive margin shows the strongest association with prognosis, supported by clinicopathological correlation and nomogram-based survival prediction.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

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Background

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Introduction

TYPE Original Research PUBLISHED 13 August 2024 DOI 10.3389/fimmu.2024.1423775 OPEN ACCESS EDITED BY Ying Ma, Tianjin Medical University Cancer Institute and Hospital, China REVIEWED BY Feng Wei, Tianjin Medical University Cancer Institute and Hospital, China Luis Munoz-Erazo, The University of Auckland, New Zealand *CORRESPONDENCE Hui Zhao [zhaohui@dmu.edu.cn](zhaohui@dmu.edu.cn) †These authors have contributed equally to this work RECEIVED 26 April 2024 ACCEPTED 24 July 2024 PUBLISHED 13 August 2024 CITATION Xin S, Wen S, He P, Zhao Y and Zhao H (2024) Density of tertiary lymphoid structures and their correlation with prognosis in non-small cell lung cancer. Front. Immunol. 15:1423775 . doi: 10.3389/fimmu.2024.1423775 COPYRIGHT © 2024 Xin, Wen, He, Zhao and Zhao. This isan open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Density of tertiary lymphoid structures and their correlation with prognosis in non-small cell lung cancer Shuyue Xin 1†, Shuang Wen 2†, Peipei He 1†, Yulong Zhao 1 and Hui Zhao 1* 1 Department of Health Examination Center, The Second Afﬁliated Hospital of Dalian Medical University, Dalian, China, 2 Department of Pathology, The Friendship Hospital of Dalian, Dalian, China Background: Tertiary lymphoid structures (TLS), ordered structure of tumorinﬁltrating immune cells in tumor immune microenvironment (TIME), play an important role in the development and anti-tumor immunity of various cancers, including liver, colon, and gastric cancers. Previous studies have demonstrated that the presence of TLS in intra-tumoral (IT), invasive margin (IM), and peritumoral (PT) regions of the tumors at various maturity statuses. However, the density of TLS in different regions of non-small cell lung cancer (NSCLC) has not been extensively studied. Methods: TLS and tumor-inﬁltrating immune cells were assessed using immunohistochemistry (IHC) staining in 82 NSCLC patients. Tumor samples were divided into three subregions as IT, IM and PT regions, and TLS were identiﬁed as early/primary TLS (E-TLS) or secondary/follicular TLS (F-TLS) . The distribution of TLS in different maturity statuses, along with their correlation with clinicopathological characteristics and prognostic value, was assessed. Nomograms were used to predict the probability of 1-, 3-, and 5-year overall survival (OS) in patients with NSCLC. Results: The density of TLS and proportion of F-TLS in the IT region (90 . 2%, 0.45/mm2, and 61 . 0%, respectively) were signiﬁcantly higher than those in the IM region (72 . 0%, 0 .18/mm2, and 39 . 0%, respectively) and PT region (67 . 1%, 0.16/mm2, and 40 . 2%, respectively) . A lower density of TLS, especially E-TLS in the IM region, was correlated with better prognosis in NSCLC patients. CD20+ B cells, CD3+ T cells, CD8+ cytotoxic T cells, and CD68+ macrophages were signiﬁcantly overexpressed in the IM region. CD20+ B cells and CD3+ T cells in the IM region were signiﬁcantly correlated with the density of E-TLS, while no statistically signiﬁcant correlation was found with F-TLS. The E-TLS density in the IM region and TNM stage were independent prognostic factors for NSCLC patients. Thenomogram showed good prognostic ability. Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) Conclusions: A higher density of E-TLS in the IM region was associated with a worse prognosis in NSCLC patients, potentially due to the inhibition of TLS maturation caused by the increased density of suppressive immune cells at the tumor invasion front. KEYWORDS tertiary lymphoid structures (T

FAQs

What are tertiary lymphoid structures (TLS) in the context of NSCLC?

TLS are ordered structures formed by tumor-infiltrating immune cells within the tumor immune microenvironment, including T cells and B cells, along with other immune and stromal components at the periphery.

How were TLS density and maturity assessed in this study?

TLS were measured by immunohistochemistry in 82 NSCLC patients. Tumor regions were divided into intra-tumoral, invasive margin, and peritumoral areas, and TLS were classified as early/primary (E-TLS) or secondary/follicular (F-TLS).

Which TLS feature was linked to prognosis and why could that matter?

Lower TLS density—especially E-TLS—in the invasive margin correlated with better prognosis. The authors suggest that higher E-TLS density in the invasive margin may worsen outcomes by inhibiting TLS maturation due to suppressive immune cells at the tumor invasion front.

Sep 22, 2026

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