ArticleCell death & disease2024
Inhibition of furin in CAR macrophages directs them toward a proinflammatory phenotype and enhances their antitumor activities.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Multi-cell death gene signature predicts lung adenocarcinoma prognosis and reveals FURIN regulates ferroptosis via NRF2-xCT-GPX4 axis.Respiratory research · 2026Article
- Chimeric antigen receptor-macrophages: A new paradigm for cell therapy.Bioengineering & translational medicine · 2026Review
- Cell-based cancer immunotherapy: milestones, mechanistic insights, and emerging therapeutic directions.Acta pharmacologica Sinica · 2026Review
- Article
- Humoral immunity in cancer.Signal transduction and targeted therapy · 2026Review
- 25 Years of Cancer Immunoediting: Dendritic Cells and Macrophages Filled the Missing Gap.Cancers · 2026Review
- The Role of Furin in Hallmarks of Aneurysms: A Focus On Its Substrates.Current atherosclerosis reports · 2026Review
- Chimeric Antigen Receptor-Immune Cell-Based Therapies for Clear Cell Renal Cell Carcinoma: Latest Advancements and Directions.Cancers · 2026Review
- CAR-engineering of innate and innate-like immune cells: a new horizon in adoptive cell therapy for solid tumors.Journal for immunotherapy of cancer · 2026Review
- Optimizing next-generation CAR-macrophages against solid tumors: challenges and potential strategies.Journal of hematology & oncology · 2026Review
- Synthetic SIGLEC9-based chimeric switch receptor augments the efficacy of CAR macrophages against glioblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- CAR-engineered cell therapies: current understandings and future perspectives.Molecular biomedicine · 2026Review
- Innate immune cells in chimeric antigen receptor therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Decoding the spatiotemporal dynamics of tumor immune niche remodeling in cancer immunotherapy.Frontiers in immunology · 2026Review
- A Myeloid-Specific Endogenous TRP1-CAR Knock-in Mouse Model for Melanoma-Targeted Immunotherapy.ImmunoTargets and therapy · 2026Article
- CD86 costimulation enhances the antitumor activity of NKG2D CAR-Macrophages and synergizes with Anti-PD-L1 therapy to suppress prostate cancer progression.Cell communication and signaling : CCS · 2025Article
- Harnessing chimeric antigen receptor macrophages against solid tumors.Cancer communications (London, England) · 2025Review
- CAR-Macrophage Cell Therapy: A New Era of Hope for Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Macrophage polarization: molecular mechanisms, disease implications, and targeted therapeutic strategies.Frontiers in immunology · 2025Review
- Unleashing the power of CAR-M therapy in solid tumors: a comprehensive review.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR)-T-cell therapy has revolutionized cellular immunotherapy, demonstrating remarkable efficacy in hematological cancers. However, its application in solid tumors faces significant challenges, including limited T-cell infiltration and tumor-induced immunosuppression. Given the prominent role of macrophages in the tumor microenvironment, their phenotypic plasticity and inherent antitumor properties, such as phagocytosis, offer a promising avenue for therapeutic intervention. This study focuses on the development of a second generation of CAR macrophages (CAR-Ms). We elucidated the role of the proprotein convertase furin in macrophages, demonstrating its overexpression in the presence of tumor cells. Importantly, furin inhibition maintains a proinflammatory macrophage phenotype, potentially redirecting them towards an antitumor state. Compared to furin-expressing counterparts, furin-inhibited CAR-Ms exhibited heightened antitumor phagocytic activity against breast cancer cells and ex vivo patient-derived tumoroids. Notably, they sustained a persistent proinflammatory profile, indicative of enhanced tumoricidal potential. Additionally, furin-inhibited CAR-Ms secreted factors that promote T-cell activation, offering a means to modulate the tumor microenvironment. In summary, our work highlights the translational potential of furin-inhibited CAR-Ms as a potent cellular therapy to mitigate macrophage exhaustion within the tumor environment. By capitalizing on macrophage-mediated antitumor responses, these findings pave the way for the development of second-generation CAR-M therapeutic strategies tailored for solid tumors.
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