Evidence map›Paper›PMID 41205596›Full record

ArticleCell reports. Medicine2025

Therapeutic stress triggers tumor STAT1 acetylation to disarm immunotherapy.

Po-Hsien Chiu, Kuan-Chen Lai, Hung-Ling Wang, Yao-Wen Chang, Wen-Chi Wu, Tien-Hua Chen, Yu-Shuen Tsai, Jie-Hong Song, Nai-Yun Sun, Gar-Yang Chau and 22 more

Abstract read
PubMed Full text at PMC Publisher
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Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

2 citing papers in PubMed.

  1. Article
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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

32 authors.

Po-Hsien ChiuProgram in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei 112304, Taiwan.
Kuan-Chen LaiInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Hung-Ling WangCenter for Molecular Medicine, China Medical University Hospital, Taichung 406040, Taiwan; Research Center for Cancer Biology, China Medical University, Taichung 40402, Taiwan; Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung 40402, Taiwan.
Yao-Wen ChangInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Wen-Chi WuInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; Department of Oncology, Taipei Veterans General Hospital, Taipei 112201, Taiwan.
Tien-Hua ChenInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; Department of Oncology, Taipei Veterans General Hospital, Taipei 112201, Taiwan.
Yu-Shuen TsaiCancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Jie-Hong SongCancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Nai-Yun SunCancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Gar-Yang ChauDivision of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 112201, Taiwan.
Wen-Liang FangDivision of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 112201, Taiwan.
Ju-Pei ChenCancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Hung-Ming WangDivision of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 333423, Taiwan.
Huai-Cheng HuangDepartment of Oncology, National Taiwan University Hospital and College of Medicine, Taipei 100225, Taiwan.
Meng-Che HsiehDepartment of Hematology and Oncology, E-Da Cancer Hospital, Kaohsiung 824005, Taiwan.
Chun-Hung HuaDepartment of Otorhinolaryngology, China Medical University Hospital, Taichung 404327, Taiwan.
Ming-Yu LienDivision of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 404327, Taiwan.
Yi-Fang ChangDivision of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104217, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Taitung 950408, Taiwan.
Hui-Ching WangDivision of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan.
Chih-Yen ChienDepartment of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Doctoral Program of Clinical and Experimental Medicine, National Sun Yat-sen University, Kaohsiung 833401, Taiwan.
Tai-Lin HuangDepartment of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan.
Chen-Chi WangDepartment of Otolaryngology-Head and Neck Surgery, Taichung Veterans General Hospital, Taichung 407219, Taiwan.
Yi-Chun LiuDepartment of Radiation Oncology, Taichung Veterans General Hospital, Taichung 407219, Taiwan.
Jo-Pai ChenDepartment of Oncology, National Taiwan University Hospital Yunlin Branch, Yunlin 632007, Taiwan.
Wei-Chen LuDepartment of Oncology, National Taiwan University Hospital Yunlin Branch, Yunlin 632007, Taiwan.
Ching-Yi YiuDepartment of Otolaryngology, Yumin Medical Corporation Yumin Hospital, Caotun, Nantou 542007, Taiwan.
Chien-Liang LinDivision of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 736402, Taiwan.
Pei-Jen LouDepartment of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100225, Taiwan.
Pen-Yuan ChuDepartment of Otolaryngology, Taipei Veterans General Hospital, Taipei 112201, Taiwan.
Shao-Chun WangResearch Center for Cancer Biology, China Medical University, Taichung 40402, Taiwan; Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung 40402, Taiwan; Graduate Institute of Biomedical Sciences, Institute of Biochemistry and Molecular Biology, China Medical University, Taichung 40402, Taiwan.
Mien-Chie HungCenter for Molecular Medicine, China Medical University Hospital, Taichung 406040, Taiwan; Research Center for Cancer Biology, China Medical University, Taichung 40402, Taiwan; Graduate Institute of Biomedical Sciences, Institute of Biochemistry and Molecular Biology, China Medical University, Taichung 40402, Taiwan.
Muh-Hwa YangProgram in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei 112304, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; Department of Oncology, Taipei Veterans General Hospital, Taipei 112201, Taiwan; Department of Research and Education, Taipei City Hospital, Taipei 103212, Taiwan. Electronic address: mhyang2@nycu.edu.tw.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sequential cancer therapy presents a critical challenge, as the impact of prior treatments on immunotherapy remains unclear. Here, we demonstrate that therapeutic stress from prolonged cetuximab exposure induces tumor-intrinsic resistance to immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC). In a multicenter analysis, extended cetuximab treatment correlates with poor ICB response and survival. Mechanistically, chronic therapeutic stress provokes an initial inflammatory response that transitions into immune resistance. A previously unknown post-translational modification, STAT1 lysine 637 acetylation, serves as the molecular switch driving this process. Triggered by treatment-induced tumor necrosis factor alpha (TNF-α), this acetylation impairs STAT1 dimerization and transcriptional activity, while treatment-induced interferon (IFN)-β promotes STAT1 phosphorylation at tyrosine 701 and subsequent degradation. These modifications disrupt tumor IFN-γ responsiveness. Importantly, STAT1 acetylation in pre-treatment tumor samples predicts ICB efficacy, underscoring its potential as a clinically relevant biomarker for guiding immunotherapy decisions.

Indexed as

Head and Neck NeoplasmsImmunotherapySquamous Cell Carcinoma of Head and NeckSTAT1 Transcription FactorAcetylationAnimalsCell Line, TumorCetuximabHumansImmune Checkpoint InhibitorsInterferon-gammaMicePhosphorylationProtein Processing, Post-TranslationalCetuximabImmune Checkpoint InhibitorsInterferon-gammaSTAT1 protein, humanSTAT1 Transcription Factoracetylationimmune checkpoint blockadeinteferon gamma signalingSTAT1

Identifiers

PMID41205596
PMCPMC12711663

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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.