ArticleThe Journal of clinical investigation2025
Targeting legumain-mediated cell-cell interaction sensitizes glioblastoma to immunotherapy in preclinical models.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Review
- Galanin impairs tumor immunity in glioblastoma by promoting infiltration and ferroptosis resistance of myeloid-derived suppressor cells.Nature cancer · 2026Article
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Symbiotic exclusivity between CLOCK and TFPI2 drives stemness and immunosuppression in glioblastoma models.The Journal of clinical investigation · 2026Article
- Microglial TBK1 Signaling Promotes Breast Cancer Brain Metastasis.Cancer research · 2026Article
- Monocyte-Derived LGMNResearch (Washington, D.C.) · 2026Article
- An Emodin-Depot Microsphere-in-Hydrogel Reprograms the Immuno-myogenic Niche to Enable Volumetric Muscle Loss Repair Revealed by Single-Cell Profiling.Research (Washington, D.C.) · 2026Article
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Neuropeptide adrenomedullin remodels stemness and macrophage dynamics in glioblastoma.Cell reports · 2025Article
- Therapeutic potential of targeting macrophages and microglia in glioblastoma.Trends in pharmacological sciences · 2025Review
- ATP11B triggers the infiltration of T cells into GBM and intensifies anti-GBM immunity by upregulating and externalizing S1PR1.Journal of translational medicine · 2025Article
- Berberine suppresses hepatocellular carcinoma progression by blocking IL-4-JAK1-STAT6-mediated M2 polarization of macrophage.Frontiers in pharmacology · 2025Article
- Efficacy and survival outcomes of bevacizumab plus minocycline for glioblastoma.American journal of translational research · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Tumor-associated macrophages (TAMs) are the most prominent immune cell population in the glioblastoma (GBM) tumor microenvironment and play critical roles in promoting tumor progression and immunosuppression. Here we identified that TAM-derived legumain (LGMN) exhibited a dual role in regulating the biology of TAMs and GBM cells. LGMN promoted macrophage infiltration in a cell-autonomous manner by activating the GSK3β/STAT3 pathway. Moreover, TAM-derived LGMN activated integrin αv/AKT/p65 signaling to drive GBM cell proliferation and survival. Targeting of LGMN-directed macrophage (inhibiting GSK3β and STAT3) and GBM cell (inhibiting integrin αv) mechanisms resulted in an antitumor effect in immunocompetent GBM mouse models that was further enhanced by combination with anti-PD-1 therapy. Our study reveals a paracrine and autocrine mechanism of TAM-derived LGMN that promotes GBM progression and immunosuppression, providing effective therapeutic targets to improve immunotherapy in GBM.
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