Evidence map›Paper›PMID 42321664›Full record

ArticleBMC cancer2026

Dissecting T-cell exhaustion heterogeneity and immune ecosystem dynamics in colorectal cancer through multi-omics machine learning.

Zhijing Zhang, Peng Ouyang, Kai Cui, Jianqin Lai, Yixiang Wen, Xin Deng, Wanyu Chen, Zhenhong Xian, Qi Qi, Zhen Bao and 2 more

Abstract read
In one paragraph

Article in BMC 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.

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0citing papers in PubMed
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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Zhijing Zhang *Department of General Surgery, The First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou, 510630, China.
Peng Ouyang *Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Youth Road 23, Zhanggong District, Ganzhou City, 341000, Jiangxi Province, China.
Kai Cui *State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, 510632, China.
Jianqin Lai *Department of General Surgery, School of Medicine, the Second Affiliated Hospital of South China University of Technology (Guangzhou First People's Hospital), Guangzhou, 510180, China.
Yixiang WenDepartment of General Surgery, The First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou, 510630, China.
Xin DengDepartment of General Surgery, The First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou, 510630, China.
Wanyu Chen *Department of General Surgery, The First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou, 510630, China.
Zhenhong XianDepartment of General Surgery, The First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou, 510630, China.
Qi QiState Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, 510632, China. qiqikc@jnu.edu.cn.
Zhen BaoDepartment of General Surgery, The First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou, 510630, China. baozhen@jnu.edu.cn.
Jin GongDepartment of General Surgery, The First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou, 510630, China. zaitushuguan@163.com.
Xiao He *Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Youth Road 23, Zhanggong District, Ganzhou City, 341000, Jiangxi Province, China. hexiao00914@163.com.

Funding

Fundamental Research Funds for the Central Universities 11624305Guangdong Association for Science and Technology Youth Science and Technology Talent Development Program SKXRC2025117Guangzhou Basic Research Program City - University (Institute) - Enterprise Joint Funding Project SL2024A03J01364Medical Scientific Research Foundation of Guangdong Province of China A2023398National Natural Science Foundation of China 82504048the Bethune Charitable Foundation 803292
6 · The paper itself

Abstract

backgroundImmunotherapy has shown limited efficacy in a substantial subset of CRC patients, yet the mechanisms underlying therapeutic resistance remain incompletely understood. T-cell exhaustion (TEX) in the tumor microenvironment has been identified as a pivotal driver of immune evasion and tumor progression. Dissecting its contribution to CRC is essential for the development of rational therapeutic strategies.

methodsWe integrated scRNA-seq and bulk transcriptomic data to identify CD8⁺ T-cell exhaustion core genes via hdWGCNA and ten machine learning algorithms, constructed a multivariate Cox-based TEX score model validated across independent cohorts and immunotherapy datasets, and experimentally confirmed our findings by RT-qPCR, Western blot, and quantitative multiplex immunofluorescence in clinical CRC specimens.

resultsOur single-cell analysis revealed a continuum of intra-tumoral CD8⁺ T-cell exhaustion states, identified a five-gene TEX score (KLF3, LMNA, SLC2A3, ARL4C, TIMP1) that predicted poor prognosis and an immunosuppressive microenvironment. Further experimental validation confirmed the differential expression and spatial co-localization with CD8⁺ T cells in clinical specimens.

conclusionsOur findings implicate TEX as a central mediator of immunotherapy resistance in CRC, offering a clinically actionable framework for patient stratification and therapeutic decision-making.

Indexed as

CD8-Positive T-LymphocytesColorectal NeoplasmsMachine LearningT-Cell ExhaustionTumor MicroenvironmentGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunotherapyMultiomicsPrognosisSingle-Cell AnalysisTranscriptomeColorectal cancer (CRC)Immunotherapy sensitivityMachine learningPredictable modelT cell exhaustion (TEX)Tumor microenvironment (TME)

Identifiers

PMID42321664
PMCPMC13543431

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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.