ArticleThe EMBO journal2024
LC3-associated phagocytosis of neutrophils triggers tumor ferroptotic cell death in glioblastoma.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies.Experimental hematology & oncology · 2026Review
- Unlocking glioma vulnerabilities: targeting regulated cell death pathways for innovative therapies.Cell death discovery · 2026Review
- STING signaling pathway: An oasis in the glioblastoma immune desert.Theranostics · 2026Review
- Ferroptosis and metabolic reprogramming in the immunosuppressive microenvironment of glioblastoma: emerging mechanisms and novel strategies.Frontiers in immunology · 2026Review
- Mechanistic insights into the dynamics of plasma membrane repair in cancer.Molecular biology reports · 2025Review
- Neutrophils in cancer: At the crucial crossroads of anti-tumor and pro-tumor.Cancer communications (London, England) · 2025Review
- Complex I inhibition combined with TLR activation in the breast tumor microenvironment educates cytotoxic neutrophils.Science advances · 2025Article
- Neutrophil Engulfment in Cancer: Friend or Foe?Cancers · 2025Review
- Gut-Brain-Microbiome Axis in the Regulation of Cancer Immune Escape and Immunotherapy in Tumors.Research (Washington, D.C.) · 2025Review
- Autophagy-mediated regulation of neutrophil inflammatory responses and its relevance to central nervous system diseases.Frontiers in aging neuroscience · 2025Review
- Procyanidin B1 Promotes PSMC3-NRF2 Ubiquitination to Induce Ferroptosis in Glioblastoma.Phytotherapy research : PTR · 2024Article
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Authors and funding
10 authors.
Funding
Abstract
Necrosis in solid tumors is commonly associated with poor prognostic but how these lesions expand remains unclear. Studies have found that neutrophils associate with and contribute to necrosis development in glioblastoma by inducing tumor cell ferroptosis through transferring myeloperoxidase-containing granules. However, the mechanism of neutrophilic granule transfer remains elusive. We performed an unbiased small molecule screen and found that statins inhibit neutrophil-induced tumor cell death by blocking the neutrophilic granule transfer. Further, we identified a novel process wherein neutrophils are engulfed by tumor cells before releasing myeloperoxidase-containing contents into tumor cells. This neutrophil engulfment is initiated by integrin-mediated adhesion, and further mediated by LC3-associated phagocytosis (LAP), which can be blocked by inhibiting the Vps34-UVRAG-RUBCN-containing PI3K complex. Myeloperoxidase inhibition or Vps34 depletion resulted in reduced necrosis formation and prolonged mouse survival in an orthotopic glioblastoma mouse model. Thus, our study unveils a critical role for LAP-mediated neutrophil internalization in facilitating the transfer of neutrophilic granules, which in turn triggers tumor cell death and necrosis expansion. Targeting this process holds promise for improving glioblastoma prognosis.
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