Evidence map›Paper›PMID 41912776›Full record

ArticleOncogene2026

Dual function of DOT1L suppresses tumor cell-intrinsic immunogenicity in hepatocellular carcinoma.

Siyuan Xu, Ruijie Gong, Songchen Liu, Jianhua Wang, Yijie Shen, Chuxuan Peng, Qin Feng, Min Luo, Fei Lan, Jia Fan and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 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

12 authors.

Siyuan XuDepartment of Systems Biology for Medicine, School of Basic Medical Sciences, Department of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Ruijie GongDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Institutes of Biomedical Sciences, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
Songchen LiuDepartment of Systems Biology for Medicine, School of Basic Medical Sciences, Department of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Jianhua WangDepartment of Systems Biology for Medicine, School of Basic Medical Sciences, Department of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Yijie ShenDepartment of Systems Biology for Medicine, School of Basic Medical Sciences, Department of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Chuxuan PengDepartment of Systems Biology for Medicine, School of Basic Medical Sciences, Department of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Qin FengDepartment of Systems Biology for Medicine, School of Basic Medical Sciences, Department of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Min LuoInstitute of Pediatrics of Children's Hospital of Fudan University, the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0001-5732-4848
Fei LanShanghai Key Laboratory of Medical Epigenetics, State International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-8559-7146
Jia FanDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Institutes of Biomedical Sciences, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0001-5158-629X
Jiabin CaiDepartment of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Institutes of Biomedical Sciences, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China. cai.jiabin@zs-hospital.sh.cn.
Xianjiang LanDepartment of Systems Biology for Medicine, School of Basic Medical Sciences, Department of Hepatobiliary Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China. xianjiang_lan@fudan.edu.cn.ORCID http://orcid.org/0000-0001-8208-2916

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32370614National Natural Science Foundation of China (National Science Foundation of China) 82272703National Natural Science Foundation of China (National Science Foundation of China) 82473201
6 · The paper itself

Abstract

Immune checkpoint blockade (ICB) therapy for many cancers remains limited in patients' overall response rate. Discovery and development of more effective combinatorial approaches is urgent. Here, through CRISPR/Cas9 genetic screens, we identify DOT1L as a versatile epigenetic factor that functions to suppress tumor-intrinsic immunity through a dual mechanism. Depletion of DOT1L induces the expression of transposable elements and subsequent type I interferon (IFN) response, and meanwhile lowers ZEB1 levels to further unleash the expression of immune-related genes. In turn, we demonstrate that DOT1L loss or treatment with the clinical stage inhibitor EPZ-5676 sensitizes tumors to ICB with increased immune infiltration in mice. More importantly, EPZ-5676 treatment alone is sufficient to enhance antitumor immunity in humanized mice. TCGA data analysis reveals an inverse correlation between DOT1L expression and IFN signatures across multiple cancer types. These findings provide a rationale for targeting DOT1L to improve tumor immunogenicity and overcome immunotherapy resistance.

Indexed as

Carcinoma, HepatocellularHistone-Lysine N-MethyltransferaseLiver NeoplasmsAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansImmune Checkpoint InhibitorsMiceDOT1L protein, humanHistone-Lysine N-MethyltransferaseImmune Checkpoint Inhibitors

Identifiers

PMID41912776

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.