ArticleCell reports. Medicine2026
HE4 drives PD-L1 expression in myeloid cells via IFN-γR-JAK-STAT3 signaling to promote tumor immune evasion.
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Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- VSIG4 suppresses antitumor T cell immunity via the SLC3A2-dependent metabolic-ionic checkpoint.Journal for immunotherapy of cancer · 2026Article
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Authors and funding
19 authors.
Bo ZengThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China. Electronic address: zengbo92@163.com.
Yingying ZhouThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Heping WangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Panyin ShuSchool of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Ting PanSchool of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Fangfang LiuDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yangyang LiThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Ming YiThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Ruirui HeThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China; Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, Chengdu 610072, China.
Lingyun FengThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Zhihui CuiThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Guoling HuangSchool of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Yanyun DuThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China; Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, Chengdu 610072, China.
Xi LiSchool of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
Chuwen ChenWest China Second University Hospital of Sichuan University, Chengdu, Sichuan, China.
Qian ChuDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yuan WangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China. Electronic address: wangyuan_med@uestc.edu.cn.
Xue XiaoDepartment of Pathology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China. Electronic address: xiaoxue@med.uestc.edu.cn.
Chenhui WangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China; Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, Chengdu 610072, China; Chuan-Yu Joint Key Laboratory for Pathological and Laboratory Medicine, Jinfeng Laboratory, Chongqing 400039, China. Electronic address: wangch@uestc.edu.cn.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have achieved clinical success, yet most patients fail to respond and many develop immune-related adverse events (irAEs). Although interferon gamma (IFN-γ) is considered the canonical driver of PD-L1 expression, regulation of PD-L1 in myeloid cells within the tumor microenvironment (TME) remains poorly defined. Here, we identify human epididymis protein 4 (HE4), a tumor-secreted glycoprotein overexpressed in multiple cancers, as an unrecognized inducer of myeloid PD-L1 transcription. HE4 directly binds IFN-γ receptors, activates JAK-STAT3 signaling, and upregulates PD-L1. Neutralization of mouse or human HE4 with monoclonal antibodies reduced myeloid PD-L1 expression, restored CD8
Indexed as
B7-H1 AntigenJanus KinasesMyeloid CellsReceptors, InterferonSTAT3 Transcription FactorTumor EscapeWAP Four-Disulfide Core Domain Protein 2AnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansImmune EvasionMiceSignal TransductionTumor MicroenvironmentB7-H1 AntigenCD274 protein, humanJanus KinasesReceptors, InterferonSTAT3 protein, humanSTAT3 Transcription FactorWAP Four-Disulfide Core Domain Protein 2WFDC2 protein, humananti-tumor immunityhuman epididymis protein 4IFN-γR-JAK-STAT3 axisimmune-related adverse eventsprogrammed cell death ligand 1tumor immune evasion
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