Spatial and maturational characterisation of tertiary lymphoid structures predicts immunotherapy response in extensive-stage small cell lung cancer.
4 affiliations
- 1Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan China.
- 2Department of Radiation Oncology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China.
- 3Department of Pathology The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital Jinan Shandong China.
- 4Department of Radiation Oncology, Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan China.
Abstract
Objectives
Extensive-stage small cell lung cancer (ES-SCLC) remains an aggressive malignancy with limited durable responses to immune checkpoint inhibitors (ICIs) and no established predictive biomarkers. This study aimed to evaluate the prognostic and predictive value of tertiary lymphoid structures (TLSs) in patients with ES-SCLC receiving ICI-based therapy.Methods
In this multicenter retrospective study of 180 treatment-naïve ES-SCLC patients subsequently receiving ICI-based therapy, TLSs were systematically evaluated using H&E staining, multiplex immunofluorescence, and spatial analysis to determine their prognostic and predictive value.Results
TLSs were identified in 22.2% of cases and independently associated with improved overall survival (OS) in both univariate (HR = 0.365, 95% CI: 0.217-0.613, P < 0.001) and multivariate (HR = 0.337, 95% CI: 0.199-0.569, P < 0.001) analyses. Crucially, TLS maturation status was associated with clinical outcomes, as patients with mature TLSs containing CD21⁺ follicular dendritic cells and organized germinal centers experienced significantly longer survival than those with non-mature TLSs (P = 0.0049). Beyond mere presence, responders to ICIs exhibited distinct spatial characteristics, including higher TLS densities, denser immune infiltration, and shorter distances between TLS-resident CD20⁺ B cells, CD3⁺ T cells, and tumor cells, suggesting that immune-tumor spatial organization within TLSs reflects functional antitumor engagement.Conclusion
TLS maturation and spatial architecture may serve as candidate tissue biomarkers associated with clinical outcomes in ICI-treated ES-SCLC, warranting prospective validation alongside SCLC molecular subtyping.
Related
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BibTeX
@article{wang2026spatial,
title = {{Spatial and maturational characterisation of tertiary lymphoid structures predicts immunotherapy response in extensive-stage small cell lung cancer.}},
author = {Haoyu Wang and Xiaoling Shang and Yuanzhu Jiang and Chenglong Zhao and Zhenxiang Li and Chufeng Zhang and Qinhao Xu and Shanshan Du and Jiamao Lin and Haiyong Wang},
journal = {Clinical \& translational immunology},
year = {2026},
month = oct,
doi = {10.1002/cti2.70125},
url = {https://europepmc.org/article/MED/42903730},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Spatial and maturational characterisation of tertiary lymphoid structures predicts immunotherapy response in extensive-stage small cell lung cancer.
AU - Haoyu Wang
AU - Xiaoling Shang
AU - Yuanzhu Jiang
AU - Chenglong Zhao
AU - Zhenxiang Li
AU - Chufeng Zhang
AU - Qinhao Xu
AU - Shanshan Du
AU - Jiamao Lin
AU - Haiyong Wang
PY - 2026
DA - 2026/10/20
JO - Clinical & translational immunology
DO - 10.1002/cti2.70125
UR - https://europepmc.org/article/MED/42903730
AB - Objectives Extensive-stage small cell lung cancer (ES-SCLC) remains an aggressive malignancy with limited durable responses to immune checkpoint inhibitors (ICIs) and no established predictive biomarkers. This study aimed to evaluate the prognostic and predictive value of tertiary lymphoid structures (TLSs) in patients with ES-SCLC receiving ICI-based therapy.Methods In this multicenter retrospective study of 180 treatment-naïve ES-SCLC patients subsequently receiving ICI-based therapy, TLSs were systematically evaluated using H&E staining, multiplex immunofluorescence, and spatial analysis to determine their prognostic and predictive value.Results TLSs were identified in 22.2% of cases and independently associated with improved overall survival (OS) in both univariate (HR = 0.365, 95% CI: 0.217-0.613, P < 0.001) and multivariate (HR = 0.337, 95% CI: 0.199-0.569, P < 0.001) analyses. Crucially, TLS maturation status was associated with clinical outcomes, as patients with mature TLSs containing CD21⁺ follicular dendritic cells and organized germinal centers experienced significantly longer survival than those with non-mature TLSs (P = 0.0049). Beyond mere presence, responders to ICIs exhibited distinct spatial characteristics, including higher TLS densities, denser immune infiltration, and shorter distances between TLS-resident CD20⁺ B cells, CD3⁺ T cells, and tumor cells, suggesting that immune-tumor spatial organization within TLSs reflects functional antitumor engagement.Conclusion TLS maturation and spatial architecture may serve as candidate tissue biomarkers associated with clinical outcomes in ICI-treated ES-SCLC, warranting prospective validation alongside SCLC molecular subtyping.
SN - 2050-0068
ER -