ArticleNature communications2025
USP2 inhibition unleashes CD47-restrained phagocytosis and enhances anti-tumor immunity.
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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 23 papers.
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23citing papers in PubMed
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Who cites it
23 citing papers in PubMed.
- M2-Exo-derived miR-1227-5p protects against periodontitis through inhibiting USP2-dependent deubiquitination of Drp1.Journal of bioenergetics and biomembranes · 2026Article
- Role of DLL4 in Neutrophil Aging and Impaired Clearance in Sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Ubiquitin-driven regulation of immune checkpoints in lung cancer: Mechanisms and therapeutic implications (Review).Experimental and therapeutic medicine · 2026Review
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Chemotherapy-Activated GSK3β-DNMT1 Signaling Upregulates CD47 to Evade Macrophage Phagocytosis and Drive Temozolomide Resistance in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Alantolactone inhibits T-cell lymphoma progression by suppressing CD47 expression via the PI3K/AKT and ERK signaling pathways.Apoptosis : an international journal on programmed cell death · 2026Article
- Integrated WGCNA, Network Pharmacology, and UPLC-MS/MS Profiling for Investigating the Antitumor Effects of the Kansui Radix Dichloromethane Fraction Against Renal Cell Carcinoma with Experimental Validation.International journal of molecular sciences · 2026Article
- Targeting the CD47-SIRPα phagocytic checkpoint in cancer: Biology, translational opportunities, and next-generation therapeutic strategies.Smart molecules : open access · 2026Review
- CD90 mediates gastric cancer immune evasion though regulating IGF2BP2 to stabilize the m6A-CD47/SIRPα axis.Cancer cell international · 2026Article
- Endothelial USP2a-METTL16 loop potentiates IL-6 signaling via mCell death and differentiation · 2026Article
- PRMT1-mediated asymmetric dimethylation of arginine residue 602 in DDX1 promotes cholangiocarcinoma progression.Clinical and molecular hepatology · 2026Article
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Ubiquitin-Specific Protease 2 (USP2) as a Modulator of Energy Metabolism: A Review of Studies Using Animal and Cellular Models.Biomedicines · 2026Review
- Downregulation of B7-H4 contributes to the synergistic effect of USP2a-targeted/anti-PD-1 combination therapy in EGFR mutant lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- ML364 ameliorates NLRP3-induced inflammatory response.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Construction of a ubiquitination-related gene signature to predict prognosis and treatment response in lung adenocarcinoma.Pakistan journal of medical sciences · 2026Article
- Ir(III) Complexes Convert Cold to Hot Tumors via Ferroptosis/Necroptosis-Driven Immunogenic Cell Death and Photosensitized CD47 Downregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CDK10 suppresses nucleic acid sensors-mediated antitumor immunity.Nature cancer · 2026Article
- CD47 destabilization via manipulating the SPOP-USP2 axis augments macrophage phagocytosis and cancer immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
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Authors and funding
24 authors.
Panpan Dai *Department of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Yishuang Sun *Department of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Zhengrong Huang *Tumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Yu-Tong Liu *State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Minling GaoDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Hai-Ming LiuState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Jie ShiDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Chuan HeDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Bolin XiangDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Yingmeng YaoDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Haisheng YuDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Gaoshan XuDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Lijun KongDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Xiangling XiaoDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.ORCID http://orcid.org/0000-0002-5352-3441
Xiyong WangDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Xue ZhangDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Wenjun XiongDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Jing HuDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Dandan LinCancer Center, Renmin Hospital of Wuhan University, Wuhan, China.ORCID http://orcid.org/0000-0003-3843-6945
Bo ZhongState Key Laboratory of Metabolism and Regulation in Complex Organisms, College of Life Sciences, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.ORCID http://orcid.org/0000-0002-3832-2895
Gang ChenState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. geraldchan@whu.edu.cn.ORCID http://orcid.org/0000-0003-3332-3511
Yan GongTumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China. yan.gong@whu.edu.cn.ORCID http://orcid.org/0000-0002-4805-0459
Conghua XieDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China. chxie_65@whu.edu.cn.ORCID http://orcid.org/0000-0001-6623-9864
Jinfang ZhangDepartment of Radiation and Medical Oncology, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China. jinfang_zhang@whu.edu.cn.ORCID http://orcid.org/0000-0001-8487-6007
Funding
National Natural Science Foundation of China (National Science Foundation of China) 82273062
Abstract
The CD47/SIRPα axis conveys a 'don't eat me' signal, thereby thwarting the phagocytic clearance of tumor cells. Although blocking antibodies targeting CD47 have demonstrated promising anti-tumor effects in preclinical models, clinical trials involving human cancer patients have not yielded ideal results. Exploring the regulatory mechanisms of CD47 is imperative for devising more efficacious combinational therapies. Here, we report that inhibiting USP2 prompts CD47 degradation and reshapes the tumor microenvironment (TME), thereby enhancing anti-PD-1 immunotherapy. Mechanistically, USP2 interacts with CD47, stabilizing it through deubiquitination. USP2 inhibition destabilizes CD47, thereby boosting macrophage phagocytosis. Single-cell RNA sequencing shows USP2 inhibition reprograms TME, evidenced by increasing M1 macrophages and CD8
Indexed as
CD47 AntigenNeoplasmsPhagocytosisUbiquitin ThiolesteraseAnimalsCD8-Positive T-LymphocytesCell Line, TumorFemaleHumansImmunotherapyMacrophagesMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorTumor MicroenvironmentUbiquitinationCD47 AntigenCD47 protein, humanProgrammed Cell Death 1 ReceptorUbiquitin Thiolesterase
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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.