Evidence map›Paper›PMID 42303776›Full record

ArticleNature cancer2026

Targeting PID1 generates oxysterols to switch macrophage cell fates for improved antitumor immunity.

Yuxiao Zheng, Qi Wang, Chen Dong, Qiong Wang, Mingshun Han, Haiqing Zhao, Shuang Wang, Longlong Chen, Xiaoli Zhang, Dan Yang and 15 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature 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.

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

25 authors.

Yuxiao Zheng *State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-4305-4223
Qi Wang *State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai, China.
Chen DongState Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Qiong WangState Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Mingshun HanState Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0009-0003-3636-5845
Haiqing ZhaoState Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Shuang WangState Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Longlong ChenState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0009-0008-0359-076X
Xiaoli ZhangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0009-0005-1405-8793
Dan YangHubei Key Laboratory of Sports Injury and Precision Therapy, Wuhan Fourth Hospital, Wuhan, China.ORCID http://orcid.org/0000-0002-7870-6383
Jun XiaoDepartment of Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.
Zhihuan ChewState Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0009-0001-5074-0109
Zhenfei XieState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Lei YangState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0009-0002-5491-8995
Jinyong FanState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0009-0007-1359-2518
Xin ZhengKey Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
Dezhen TuInnovative Institute of Tumor Immunity and Medicine, Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Weiyun LiState Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Lingming ZhengState Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-0104-342X
Lijian HuiThe Research Laboratory of Liver Molecular Pathology, Key Laboratory of Multi-cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-6213-6187
Xiaowu HuangLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Jinsong LiKey Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
Huiru TangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai, China. huiru_tang@fudan.edu.cn.ORCID http://orcid.org/0000-0002-7139-2756
Bin WeiInstitute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. weibin@fudan.edu.cn.ORCID http://orcid.org/0000-0002-2731-489X
Hongyan WangState Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. hongyanwang@sibcb.ac.cn.ORCID http://orcid.org/0000-0002-5781-3745

Funding

Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2023YFC2306500Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2024YFA1803100Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2024YFA1803100, 2023YFA1800203National Natural Science Foundation of China (National Science Foundation of China) 82303154National Natural Science Foundation of China (National Science Foundation of China) 82425102, 32221002
6 · The paper itself

Abstract

Disordered cholesterol-oxysterol profiles are observed in the tumor microenvironment, yet their roles in tumor-associated macrophages (TAMs) remain underexplored. This study reveals that TAMs across human pan-cancers exhibit elevated phosphotyrosine interaction domain-containing protein 1 (PID1) expression and prominent immunosuppressive gene signatures. PID1 deficiency in myeloid cells upregulates low-density lipoprotein (LDL) receptor expression, thereby promoting LDL uptake and intracellular accumulation of free cholesterol and reactive oxygen species (ROS). Increased ROS drives cholesterol oxidation to generate the oxysterols 5α,6α-epoxycholesterol (5α,6α-EC) and 7β-hydroxycholesterol (7β-OHC), which inhibit mTOR-STAT6 signaling in macrophages. Pid1 deletion switches immunosuppressive macrophages toward an antitumor subtype that downregulates arginase 1 expression while upregulating proinflammatory cytokines, thereby potentiating CD8

Indexed as

MacrophagesNeoplasmsOxysterolsTumor-Associated MacrophagesAnimalsCholesterolHumansMiceReactive Oxygen SpeciesSignal TransductionTumor MicroenvironmentCholesterolOxysterolsReactive Oxygen Species

Identifiers

PMID42303776

What OpenQuestion 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 OpenQuestion graph.