Evidence map›Paper›PMID 42468992›Full record

ArticleJournal for immunotherapy of cancer2026

Spatial architecture of tertiary lymphoid structures represents an independent prognostic dimension in hepatocellular carcinoma.

Wei Liu, Chunbin Zhu, Zihang Cui, Jieyi Shi, Boan Zhang, Anan Xiong, Liming Wang, Qiang Gao, Guangyu Ding, Xiyang Liu

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Wei LiuSchool of Computer Science and Technology, Xidian University, Xi'an, Shaan Xi, China.ORCID http://orcid.org/0009-0002-2524-1647
Chunbin ZhuDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0009-0008-9580-6600
Zihang CuiSchool of Computer Science and Technology, Xidian University, Xi'an, Shaan Xi, China.ORCID http://orcid.org/0009-0005-6763-2672
Jieyi ShiDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-8196-4498
Boan ZhangSchool of Computer Science and Technology, Xidian University, Xi'an, Shaan Xi, China.ORCID http://orcid.org/0009-0000-6049-2666
Anan XiongSchool of Computer Science and Technology, Xidian University, Xi'an, Shaan Xi, China.ORCID http://orcid.org/0009-0001-7470-8189
Liming WangSchool of Computer Science and Technology, Xidian University, Xi'an, Shaan Xi, China.ORCID http://orcid.org/0000-0001-9596-8054
Qiang GaoDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Guangyu DingDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China ding.guangyu@zs-hospital.sh.cn xyliu@xidian.edu.cn.ORCID http://orcid.org/0000-0002-8431-0406
Xiyang LiuSchool of Computer Science and Technology, Xidian University, Xi'an, Shaan Xi, China ding.guangyu@zs-hospital.sh.cn xyliu@xidian.edu.cn.ORCID http://orcid.org/0000-0001-5214-3677

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsTertiary lymphoid structures (TLS) are associated with heterogeneous outcomes in hepatocellular carcinoma (HCC), but whether their anatomical context determines clinical impact remains unknown. We hypothesized that spatial compartmentalization of TLS influences their prognostic significance.

methodsWe developed SpatialDecoder, a deep learning pipeline that simultaneously segments TLS, classifies three maturation subtypes (Agg, Fol I, Fol II), and assigns spatial compartments (intratumoral, peritumoral, capsular), achieving accurate tissue segmentation (mean Dice similarity coefficient (DSC)=0.86), TLS segmentation (DSC=0.8609), and subtyping (macro Area Under the Receiver Operating Characteristic Curve (AUROC)=0.8810). Applied to 1188 resected HCC patients, it enabled large-scale spatial TLS mapping.

resultsSpatial mapping revealed a prognostic dichotomy: higher intratumoral TLS density independently predicted prolonged overall survival, whereas higher extratumoral (peritumoral and capsular) TLS density correlated with increased recurrence risk. Based on TLS distribution, we defined four spatial immune phenotypes: TLS-Enriched (high intra/low extra), TLS-Balanced (high/high), TLS-Excluded (low intra/high extra), and TLS-Deficient (low/low). These phenotypes stratified patients into a survival gradient (log-rank p<0.0001): TLS-Enriched conferred the best outcome (HR = 0.48), TLS-Excluded the worst (HR=1.80), with intermediate prognosis for the other two phenotypes. Multivariable analysis indicated independent prognostic value. Transcriptomic profiling uncovered distinct immune mechanisms across the four phenotypes.

conclusionsThis study establishes TLS spatial context as a determinant of their dualistic role in HCC immunity, providing a large-scale demonstration of opposite prognostic roles based on TLS location. The SpatialDecoder pipeline and four-phenotype framework transform TLS assessment from a binary metric into a spatially informed approach for postoperative risk stratification.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsTertiary Lymphoid StructuresFemaleHumansMaleMiddle AgedPrognosisTumor MicroenvironmentBiomarkerHepatocellular CarcinomaImmunotherapyTumor infiltrating lymphocyte - TILTumor microenvironment - TME

Identifiers

PMID42468992
PMCPMC13384185

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.