Evidence map›Paper›PMID 42115161›Full record

ArticleNature communications2026

All-trans retinoic acid destabilizes ADAR1 protein through retinoylation-mediated USP7 dissociation and improves immunotherapy in pancreatic cancer.

Ching-Fei Li, Yongkun Wei, Heng-Huan Lee, Wei-Chao Chang, Yun Xiong, Yitao Tang, Riyao Yang, Jun Yao, Huamin Wang, Xiaofei Wang and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. 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

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

2 citing papers in PubMed.

  1. Review
  2. Review
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

27 authors.

Ching-Fei LiDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. cli14@mdanderson.org.ORCID http://orcid.org/0000-0001-7844-7003
Yongkun WeiDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Heng-Huan LeeDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-7813-1292
Wei-Chao ChangCenter for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Yun XiongProteomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-8001-129X
Yitao TangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5340-1890
Riyao YangDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jun YaoDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Huamin WangDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-2038-5863
Xiaofei WangDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Minghui LiuDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-1430-7807
Jangho ParkDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jie FuDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-1794-1360
Ying-Nai WangDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5275-6729
Li-Yuan BaiDivision of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, and China Medical University, Taichung, Taiwan.
Shao-Chun WangCenter for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Cheng-Wei ChouDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-1801-4964
Jianhua LingDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yu-Yi ChuDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zhenzhen XunDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Han LiangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7633-286X
Anirban MaitraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7923-9978
Wantong YaoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-0172-7530
Dihua YuDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6231-9381
Paul J ChiaoDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7003-6605
Haoqiang YingDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. HYing@mdanderson.org.ORCID http://orcid.org/0000-0003-0616-2310
Mien-Chie HungDepartment of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. mhung@cmu.edu.tw.ORCID http://orcid.org/0000-0003-4317-4740

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

Adenosine deaminase acting on RNA 1 (ADAR1) contributes to immunotherapy resistance by suppressing interferon signaling. Therapeutic targeting of ADAR1 has not been achieved to date in clinical settings. Here, we discover all-trans retinoic acid (ATRA) promotes ADAR1 protein degradation in cancer. In addition, ATRA induces PD-L1 and combination of ATRA and PD-1 blockade reprograms tumor microenvironments to unleash antitumor immunity, thereby impeding tumor growth. Mechanistically, we identify USP7 as a key regulator for ADAR1 protein stability. ATRA disrupts USP7-ADAR1 interaction and promotes ADAR1 ubiquitination and degradation. ATRA leads to ADAR1 retinoylation, which results in disruption of USP7-ADAR1 complex. Our clinical data shows a positive correlation between USP7 and ADAR1 in various types of cancer. Overall, this study sheds light on control of ADAR1 protein turnover and proposes a mechanism-driven combination therapy using ATRA and PD-1/PD-L1 blockade to convert immunologically "cold" into "hot" tumors, holding potential for clinical translation.

Indexed as

Adenosine DeaminaseImmunotherapyPancreatic NeoplasmsRNA-Binding ProteinsTretinoinUbiquitin-Specific Peptidase 7AnimalsB7-H1 AntigenCell Line, TumorFemaleHumansMiceProteolysisTumor MicroenvironmentUbiquitinationADAR protein, humanAdenosine DeaminaseB7-H1 AntigenCD274 protein, humanRNA-Binding ProteinsTretinoinUbiquitin-Specific Peptidase 7USP7 protein, human

Identifiers

PMID42115161
PMCPMC13376933

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.