ArticleJournal for immunotherapy of cancer2025
TIPE2 deficiency enhances macrophage phagocytosis of tumor cells.
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.
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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.
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