Evidence map›Paper›PMID 41390689›Full record

ArticleNature communications2025

Targeting LRBA triggers CTLA4 degradation and antitumor immunity for cancer immunotherapy.

Xiaolu Ge, Liang Yu, Lei Zhang, Liqing Jia, Mingjing Meng, Jingquan He, Fan Bu, Yue Song, Gaorui Sun, Shiming Lv and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. 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. 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

20 authors.

Xiaolu Ge *Laboratory of Molecular Pharmacology and Drug Discovery, Institute of Chinese Materia Medica, The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine; Shanghai Key Laboratory of Pancreatic Disease, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Liang Yu *Department of Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Lei ZhangLaboratory of Molecular Pharmacology and Drug Discovery, Institute of Chinese Materia Medica, The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine; Shanghai Key Laboratory of Pancreatic Disease, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Liqing JiaDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Mingjing MengLaboratory of Molecular Pharmacology and Drug Discovery, Institute of Chinese Materia Medica, The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine; Shanghai Key Laboratory of Pancreatic Disease, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Jingquan HeDepartment of Radiotherapy, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518033, China.
Fan BuDepartment of Neurology and Psychology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518033, China.
Yue SongDepartment of Medical Laboratory Science, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Gaorui SunSuzhou Guokuang Pharm Tech. Co., Ltd, Suzhou, Jiangsu, 215000, China.
Shiming LvSuzhou Guokuang Pharm Tech. Co., Ltd, Suzhou, Jiangsu, 215000, China.
Desheng MeiSuzhou Guokuang Pharm Tech. Co., Ltd, Suzhou, Jiangsu, 215000, China.
Yutao YangSchool of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
Dakang XuDepartment of Medical Laboratory Science, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Jingfa ZhangThe International Eye Research Institute of The Chinese University of Hong Kong (Shenzhen); C-MER Dennis Lam & Partners Eye Center, C-MER International Eye Care Group, Hong Kong, 999077, China.ORCID http://orcid.org/0000-0003-0601-4342
Shengping ZhangBiomedical Translational Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255049, China.ORCID http://orcid.org/0000-0003-4088-2768
Chuangui WangBiomedical Translational Research Institute, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255049, China.
Deshui JiaLaboratory of Cancer Genomics and Biology, Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.ORCID http://orcid.org/0000-0002-2784-126X
Yongping ChenNoble Life Sciences Inc, Sykesville, Maryland, 21784, USA.
Yue GaoDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China. gaoyue@bmi.ac.cn.ORCID http://orcid.org/0000-0003-1131-5326
Baokun HeLaboratory of Molecular Pharmacology and Drug Discovery, Institute of Chinese Materia Medica, The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine; Shanghai Key Laboratory of Pancreatic Disease, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. hbk3397@gzucm.edu.cn.ORCID http://orcid.org/0000-0003-4019-4922

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81974256National Natural Science Foundation of China (National Science Foundation of China) 82002424National Natural Science Foundation of China (National Science Foundation of China) 82173870National Natural Science Foundation of China (National Science Foundation of China) 82272874
6 · The paper itself

Abstract

The lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency causes severe autoimmune diseases and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) loss in humans. However, the impact of LRBA on antitumor immunity remains understudied. Here we show the important role of LRBA in antitumor immunity and develop small molecules targeting LRBA for cancer immunotherapy. Interestingly, LRBA is negatively associated with antitumor immunity in human patients and mouse models. Using high-throughput screening and subsequent hit optimization, we discover a small molecule LC427 that facilitates the lysosomal degradation of CTLA4 and bolsters survival of activated T cells by binding directly to LRBA and inhibiting the LRBA-CTLA4 interaction. Orally administrated LC427 increases tumor-infiltrating CD8

Indexed as

Adaptor Proteins, Signal TransducingCTLA-4 AntigenImmunotherapyNeoplasmsAnimalsCD8-Positive T-LymphocytesCell Line, TumorColitisFemaleHumansLymphocytes, Tumor-InfiltratingMiceMice, Inbred C57BLProteolysisAdaptor Proteins, Signal TransducingCTLA-4 AntigenCTLA4 protein, humanCtla4 protein, mouseLRBA protein, human

Identifiers

PMID41390689
PMCPMC12815959

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.