Evidence map›Paper›PMID 41417572›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

TOPK Inhibition Promotes Anti-Tumor Immunity Via eIF4F Complex Mediated STAT1 Translation in Gastric Cancer.

Junbing Chen, Longtao Huangfu, Gangjian Wang, Xueying Wang, Huanbo Zhu, Qian Yao, Cong Chen, Xiaohuan Tang, Ting Guo, Biao Fan and 7 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

17 authors.

Junbing ChenKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, China.ORCID https://orcid.org/0000-0002-5741-1332
Longtao HuangfuKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, China.ORCID https://orcid.org/0000-0003-4185-2747
Gangjian WangKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, China.ORCID https://orcid.org/0000-0002-3054-7205
Xueying WangKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Huanbo ZhuKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Qian YaoDepartment of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Cong ChenKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Xiaohuan TangKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Ting GuoKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Biao FanDepartment of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Xingyang LiuKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Qingda LiKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Zining LiuDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China.
Ying HuBiological Sample Bank, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China.
Tianze SunDepartment of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Jiafu JiDepartment of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.ORCID https://orcid.org/0000-0001-6878-5543
Xiaofang XingState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China.ORCID https://orcid.org/0000-0002-5707-3396

Funding

China Postdoctoral Science Foundation 2025M772256National Natural Science Foundation of China 82203579National Natural Science Foundation of China 82272889National Natural Science Foundation of China 82473157National Natural Science Foundation of China 82573666National Natural Science Foundation of China 82573870Natural Science Foundation of Beijing 7222023Natural Science Foundation of Beijing L248059Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024ZD0520600Science Foundation of Peking University Cancer Hospital BJCH2025GG02Science Foundation of Peking University Cancer Hospital JC202507Science Foundation of Peking University Cancer Hospital KC2403Science Foundation of Peking University Cancer Hospital KC2507the joint fund for key projects of National Natural Science Foundation of China U23A20463
6 · The paper itself

Abstract

Immune checkpoint blockade-directed immunotherapy emerges as a revolutionary therapy in gastric cancer (GC). However, the proportion of patients who can benefit from it and its overall efficacy remain limited. Here the aim is to identify key dual-function targets that both inhibit proliferation and suppress immune evasion. Using whole genome-wide CRISPR-Cas9-based screening, the serine/threonine kinase T-lymphokine-activated killer cell-originated protein kinase (TOPK) is identified as a key regulator of PD-L1 in gastric cancer upon IFN-γ stimulation. Mechanical study is performed to explore the role of TOPK in promoting GC malignancy and immune evasion in vitro and vivo. Higher TOPK levels in tumor tissues are observed, correlated with clinical stages, efficacy and survival. Upon IFN-γ stimulation, TOPK phosphorylates eIF4F complex component eIF4A1 to increase its unwinding activity of STAT1 mRNA, enhancing STAT1 translation efficiency. This process leads to adaptive overexpression of PD-L1 and IDO1, resulting in immunometabolic suppression through PD-L1-mediated inhibition, IDO1-induced tryptophan depletion and kynurenine production. TOPK inhibitors reshape tumor immunometabolic microenvironment to trigger anti-tumor immunity in GC. The IFN-γ-TOPK-eIF4F-STAT1-PD-L1/IDO1 axis as a crucial regulator of the tumor immunometabolic microenvironment and provide novel insights into the combination of targeted therapy and immunotherapy for GC treatment.

Indexed as

Eukaryotic Initiation Factor-4FSTAT1 Transcription FactorStomach NeoplasmsAnimalsB7-H1 AntigenCell Line, TumorFemaleHumansImmunotherapyInterferon-gammaMiceB7-H1 AntigenCD274 protein, humanEukaryotic Initiation Factor-4FInterferon-gammaSTAT1 protein, humanSTAT1 Transcription Factorgastric cancerimmunometabolic microenvironmentimmunotherapyPD‐L1TOPK

Identifiers

PMID41417572
PMCPMC12955895

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Registered trials

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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.