Evidence map›Paper›PMID 41423264›Full record

ArticleJournal for immunotherapy of cancer2025

TIPE2 deficiency enhances macrophage phagocytosis of tumor cells.

Zelong Ma, Yingyue Wang, Yanlei Dong, Hong Yuan, Ruoxuan Yang, Ying Xiao, Chun Guo, Ruirui Wang, Jianing Wang, Xiaoyan Wang and 4 more

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. 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

14 authors.

Zelong MaDepartment of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.ORCID http://orcid.org/0009-0001-8909-0246
Yingyue WangDepartment of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Yanlei DongDepartment of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.ORCID http://orcid.org/0009-0006-2983-7674
Hong YuanDepartment of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Ruoxuan YangDepartment of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Ying XiaoLaboratory of Cellular and Molecular Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Chun GuoDepartment of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Ruirui WangLaboratory of Cellular and Molecular Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Jianing WangDepartment of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Xiaoyan WangDepartment of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Faliang ZhuDepartment of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Lining ZhangDepartment of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.ORCID http://orcid.org/0000-0002-8977-1148
Yuchen Fan *Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, China shiyongyu@sdu.edu.cn fanyuchen@sdu.edu.cn.
Yongyu Shi *Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China shiyongyu@sdu.edu.cn fanyuchen@sdu.edu.cn.ORCID http://orcid.org/0000-0003-1356-3219

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionUnderstanding the negative regulatory mechanisms of immune cell functions is essential for developing effective tumor immunotherapy strategies. Macrophages play a crucial role in antitumor immunity; however, the mechanisms that negatively regulate their antitumor functions remain incompletely understood. TIPE2 is known to be a critical regulator of various immune cells, but its role as a negative regulator of macrophage antitumor functions has not yet been established.

objectivesThis study aims to investigate whether TIPE2 negatively regulates the antitumor functions of macrophages and to elucidate the mechanisms involved.

methodsWe used a mouse model of hepatic tumor metastasis and a subcutaneous tumor model to evaluate the impact of TIPE2 on macrophage antitumor functions. In vitro experiments, including fluorescence microscopy and flow cytometry, were conducted to assess whether the TIPE2 deficiency enhances the phagocytic activity of macrophages against tumor cells. Additionally, we employed co-immunoprecipitation assays along with spleen tyrosine kinase (SYK) and Ras-related C3 botulinum toxin substrate 1 (RAC1) signaling blockade assays to investigate the molecular mechanisms through which TIPE2 exerts its negative regulatory effects.

resultsOur findings indicate that TIPE2 gene loss in myeloid cells inhibits hepatic tumor metastasis, which is dependent on macrophages in the liver. Furthermore, macrophages lacking TIPE2 demonstrated enhanced tumor growth inhibition in subcutaneous tumor models. In vitro, these macrophages exhibited increased phagocytic activity against tumor cells. Mechanistically, TIPE2 negatively regulates the activation of SYK and RAC1, thereby modulating the phagocytic capabilities of macrophages.

conclusionTIPE2 represents a negative regulatory mechanism for macrophage phagocytosis against tumor cells. In the future, TIPE2 may serve as a promising target to enhance the efficacy of tumor immunotherapy strategies based on macrophages.

Indexed as

Intracellular Signaling Peptides and ProteinsLiver NeoplasmsMacrophagesPhagocytosisAnimalsCell Line, TumorHumansMicerac1 GTP-Binding ProteinSyk KinaseIntracellular Signaling Peptides and Proteinsrac1 GTP-Binding ProteinSyk KinaseTIPE2 protein, mouseHepatocellular CarcinomaMacrophagesPhagocytosis

Identifiers

PMID41423264
PMCPMC12719894

What Socratic 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 Socratic graph.