Evidence map›Paper›PMID 41855857›Full record

ArticleTranslational oncology2026

Spatial remodeling of the tumor immune microenvironment in hepatocellular carcinoma with cirrhosis driven by Treg-CD8⁺T cell crosstalk via the SPP1-ITGA4 axis.

Dongdong Xue, Xinyao Qiu, Meiyu Bao, Danjun Song, Yujia Lin, Jinxia Bao, Jianmin Wu, Tao Zhou, Shan Wang, Shuai Yang and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational oncology, 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

15 authors.

Dongdong XueThe International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China; National Center for Liver Cancer, Naval Medical University, Shanghai, 200441, China.
Xinyao QiuDepartment of Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
Meiyu BaoThe International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China; National Center for Liver Cancer, Naval Medical University, Shanghai, 200441, China.
Danjun SongDepartment of Interventional Therapy, Zhejiang Cancer Hospital, Hangzhou, 310022, China; Department of Liver Surgery and Transplantation, Zhongshan Hospital, Shanghai, 200032, China.
Yujia LinDepartment of Hepatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Jinxia BaoModel Animal Research Center, Nanjing University, Nanjing, 210093, China.
Jianmin WuInstitute of Metabolism and Integrative Biology, Fudan University, Shanghai, 200433, China.
Tao ZhouThe International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China; National Center for Liver Cancer, Naval Medical University, Shanghai, 200441, China.
Shan WangThe International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China; National Center for Liver Cancer, Naval Medical University, Shanghai, 200441, China.
Shuai YangDepartment of Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
Ji HuThe International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China; National Center for Liver Cancer, Naval Medical University, Shanghai, 200441, China.
Siyun ShenThe International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China; National Center for Liver Cancer, Naval Medical University, Shanghai, 200441, China.
Jiabin CaiDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Shanghai, 200032, China. Electronic address: cai.jiabin@zs-hospital.sh.cn.
Hongyang WangThe International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China; National Center for Liver Cancer, Naval Medical University, Shanghai, 200441, China; Department of Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China. Electronic address: hywangk@vip.sina.com.
Lei ChenThe International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China; National Center for Liver Cancer, Naval Medical University, Shanghai, 200441, China; Department of Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China. Electronic address: chenlei@smmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe tumor microenvironment (TME) of hepatocellular carcinoma (HCC) is shaped by underlying liver pathology, with potentially distinct features in HCC without cirrhosis (Non-cirrHCC) compared to HCC with cirrhosis (CirrHCC); however, these background-specific differences remain incompletely understood. This study aimed to systematically characterize and compare the cellular composition, spatial organization, and immunoregulatory interactions of the TME between Non-cirrHCC and CirrHCC.

methodsTotal 278 HBV-positive cases and mapped 2,837,999 cells across 11 major cell types were applied for spatial analysis. Subsequently, we integrated the spatial data with publicly available single-cell RNA-seq datasets for downstream analysis.

resultsComparative analysis demonstrated marked differences in immune cell composition between Non-cirrHCC and CirrHCC, with CirrHCC characterized by a pronounced decline in functionally active CD8⁺ T cells. We identified 10 distinct heterotypic cellular neighborhoods (HCNs) representing the heterotypic architecture of the tumor microenvironment. Notably, CirrHCC exhibited an immunosuppressive microenvironment with increased spatial proximity between Tregs and CD8T_CD107a⁺ cells, leading to reduced CD8⁺ T cell functional signaling. Integration with single-cell RNA sequencing from public database further indicated that, in CirrHCC, Tregs preferentially interact with the CD8T_CD107a+ cells, potentially mediated by the SPP1-ITGA4 signaling axis.

conclusionIn conclusion, CirrHCC promotes a spatially organized Treg-CD8T_CD107a⁺ suppressive niche that constrains CD8⁺ T cell effector function in HCC, with SPP1-ITGA4 emerging as a potential mediating pathway.

Indexed as

CirrhosisHepatocellular carcinomaHeterotypic cellular neighborhoodsImmunoregulatorySingle cell sequencingSpatial proteomicsTumor microenvironment

Identifiers

PMID41855857
PMCPMC13014968

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.