ArticlePloS one2021
Tertiary lymphoid structures (TLS) identification and density assessment on H&E-stained digital slides of lung cancer.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Prognostic and clinicopathological significance of tertiary lymphoid structure in non-small cell lung cancer: a systematic review and meta-analysis.BMC cancer · 2024Pooled it
- Article
- GCUNet: a graph neural network-based contextual learning network for tertiary lymphoid structure semantic segmentation in whole slide image.Visual computing for industry, biomedicine, and art · 2026Article
- Article
- The formation and function of tertiary lymphoid structures.Biomarker research · 2026Review
- Deep learning-driven recognition of panoramic tumor microenvironment features in H&E sections and its application.Journal for immunotherapy of cancer · 2026Review
- Tertiary lymphoid structures in genitourinary cancers: a comprehensive review.Frontiers in oncology · 2026Review
- The biological characteristics of tertiary lymphoid structures in head and neck cancer.Frontiers in immunology · 2026Review
- Comparative Analysis of Pathology Foundation Models for Automated Detection of Tertiary Lymphoid Structures in Hematoxylin-and-Eosin-Stained Digital Pathology Images.Computational and structural biotechnology journal · 2026Article
- Spatial characterization of tertiary lymphoid structures as predictive biomarkers for immune checkpoint blockade in head and neck squamous cell carcinoma.Oncoimmunology · 2025Article
- Association of systemic inflammatory markers and tertiary lymphoid structures with pathological complete response in patients with advanced lung adenocarcinoma receiving preoperative treatment: a retrospective cohort study.Journal of thoracic disease · 2025Article
- Three-dimensional assessments are necessary to determine the true, spatially resolved composition of tissues.Cell reports methods · 2025Article
- Spatial distribution of tertiary lymphoid structures in the molecular and clinical context of non-small cell lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Genomic Characteristics Related to Histology-Based Immune Features in Breast Cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- Quantitatively defined stromal B cell aggregates are associated with response to checkpoint inhibitors in unresectable melanoma.Cell reports · 2025Article
- Integrative whole slide image and spatial transcriptomics analysis with QuST and QuPath.NPJ precision oncology · 2025Article
- Artificial intelligence-based spatial analysis of tertiary lymphoid structures and clinical significance for endometrial cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Heterogeneity of tertiary lymphoid structures predicts the response to neoadjuvant therapy and immune microenvironment characteristics in triple-negative breast cancer.British journal of cancer · 2025Article
- Article
- Unveiling immune resistance mechanisms in nasopharyngeal carcinoma and emerging targets for antitumor immune response: tertiary lymphoid structures.Journal of translational medicine · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tertiary lymphoid structures (TLS) are ectopic aggregates of lymphoid cells in inflamed, infected, or tumoral tissues that are easily recognized on an H&E histology slide as discrete entities, distinct from lymphocytes. TLS are associated with improved cancer prognosis but there is no standardised method available to quantify their presence. Previous studies have used immunohistochemistry to determine the presence of specific cells as a marker of the TLS. This has now been proven to be an underestimate of the true number of TLS. Thus, we propose a methodology for the automated identification and quantification of TLS, based on H&E slides. We subsequently determined the mathematical criteria defining a TLS. TLS regions were identified through a deep convolutional neural network and segmentation of lymphocytes was performed through an ellipsoidal model. This methodology had a 92.87% specificity at 95% sensitivity, 88.79% specificity at 98% sensitivity and 84.32% specificity at 99% sensitivity level based on 144 TLS annotated H&E slides implying that the automated approach was able to reproduce the histopathologists' assessment with great accuracy. We showed that the minimum number of lymphocytes within TLS is 45 and the minimum TLS area is 6,245μm2. Furthermore, we have shown that the density of the lymphocytes is more than 3 times those outside of the TLS. The mean density and standard deviation of lymphocytes within a TLS area are 0.0128/μm2 and 0.0026/μm2 respectively compared to 0.004/μm2 and 0.001/μm2 in non-TLS regions. The proposed methodology shows great potential for automated identification and quantification of the TLS density on digital H&E slides.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.