Evidence mapPaperPMID 42204309Full record

ArticleNature chemical biology2026

Nuclear OXCT1 attenuates histone β-hydroxybutyrylation-mediated MHC-I transcription.

Zhiqiang Hu, Wei Lv, Ting Wen, Junyi Sun, Guimei Ji, Shuo Ru, Xue Sun, Zheng Wang, He Ren, Yudi Zhang and 18 more

Abstract read
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In one paragraph

Article in Nature chemical biology, 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

28 authors.

Zhiqiang Hu *Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.ORCID http://orcid.org/0000-0003-1313-3470
Wei Lv *HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Ting Wen *Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Junyi Sun *Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Guimei Ji *Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Shuo RuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Xue SunDepartment of Oncology Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Zheng WangZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
He RenDepartment of Oncology Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Yudi ZhangZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Pengkun ChenZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Linlin ZhouDepartment of Oncology Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Shiqi WuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Xiaoqian JiaZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Shanshuo LiuDepartment of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zheng ZhuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Jiawei XuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Tong LiuDepartment of Oncology Surgery, Harbin Medical University Cancer Hospital, Harbin, China.ORCID http://orcid.org/0000-0001-9234-1328
Yuxiong FengZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.ORCID http://orcid.org/0000-0002-9086-4448
Gaopeng LiDepartment of Colorectal Surgery and Oncology of the Second Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Yuan DingDepartment of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangu, China.
Yuhao WangZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.ORCID http://orcid.org/0000-0002-4539-3720
Yang LuoDepartment of Laboratory Medicine, Chongqing General Hospital, School of Medicine, Chongqing University, Chongqing, China.
Chang LiuInstitute of Modern Biology, Nanjing University, Nanjing, China.
Zhimin LuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.ORCID http://orcid.org/0000-0002-2859-2736
Zhigang RenDepartment of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. fccrenzg@zzu.edu.cn.ORCID http://orcid.org/0000-0003-0798-3444
Sheng-Zhong DuanStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China. duansz2008@hotmail.com.ORCID http://orcid.org/0000-0002-4866-3167
Daqian XuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China. xudaqian@zju.edu.cn.ORCID http://orcid.org/0000-0003-0478-2997

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32470815National Natural Science Foundation of China (National Science Foundation of China) 82030074National Natural Science Foundation of China (National Science Foundation of China) 82173114National Natural Science Foundation of China (National Science Foundation of China) 82188102National Natural Science Foundation of China (National Science Foundation of China) 82372814National Natural Science Foundation of China (National Science Foundation of China) 82402048National Natural Science Foundation of China (National Science Foundation of China) 82470654National Natural Science Foundation of China (National Science Foundation of China) U25A20112Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation) LD22H160002Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation) LMS25H160018Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation) LR25H160003Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation) LR26H160003
6 · The paper itself

Abstract

Understanding of the metabolic determinants influencing immunotherapy responsiveness remains limited. Here we performed a multiomics analysis of tumor biopsies from patients with hepatocellular carcinoma (HCC) treated with immune checkpoint blockade (ICB) and revealed that heightened expression of OXCT1, a rate-limiting enzyme in ketone body metabolism, was negatively correlated with ICB efficacy, whereas its metabolic substrate, β-hydroxybutyrate (BHB), displayed an opposite effect. Mechanistically, glucose deprivation in HCC cells promotes AMPK-mediated OXCT1 S113 phosphorylation, which exposes the nuclear localization sequence of OXCT1 to trigger its nuclear translocation. Nucleus-translocated OXCT1 associates with IRF1 to locally consume BHB and suppress histone H3K9 BHB at the major histocompatibility complex class I (MHC-I) and chemokine gene loci, leading to repressed transcription of these immune genes. Targeting the AMPK-OXCT1-IRF1 axis sensitizes tumor cells to ICB upon ketogenic diet. These findings reveal a mechanism by which a non-canonical function of nuclear OXCT1 coordinates the interplay between ketone body metabolic reprogramming and immunotherapy responsiveness.

Identifiers

PMID42204309

What Socratic holds

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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 Socratic graph.