ArticleEMBO molecular medicine2024
Bcl-xL targeting eliminates ageing tumor-promoting neutrophils and inhibits lung tumor growth.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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.
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.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- CAR-engineered neutrophils derived from induced pluripotent stem cells: a new frontier in cellular immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Targeted delivery of senolytic drugs using macrophage membrane-camouflaged magnetic nanoparticles inhibits endplate sclerosis.Journal of advanced research · 2026Article
- Bcl-xL blockade targets neutrophils and synergizes with chemotherapy in lung squamous cell carcinoma.EMBO molecular medicine · 2026Article
- Understanding the dual role of granulocyte-macrophage colony-stimulating factor in the lung cancer tumor microenvironment and its therapeutic implications.Translational lung cancer research · 2026Review
- Multiomics immune profiling of a patient-relevant orthotopic lung cancer model using SEPARATE-Seq.Nature communications · 2026Article
- Article
- CAR-engineered cell therapies: current understandings and future perspectives.Molecular biomedicine · 2026Review
- CD300ld blockade overcomes PMN-MDSC-mediated vaccine resistance in advanced tumors.Journal for immunotherapy of cancer · 2026Article
- PROTAC-mediated degradation of Bcl-xL potentiates target therapy in preclinical melanoma models.Journal of experimental & clinical cancer research : CR · 2026Article
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7Oncoimmunology · 2025Article
- [Molecular Mechanism of Neutrophils Driving the Progression of Lung Adenocarcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Immunosenescence and cancer: molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges.Journal of hematology & oncology · 2025Review
- Target neutrophil heterogeneity and plasticity in cancer.Journal of hematology & oncology · 2025Review
- Endoplasmic reticulum stress-related genes contribute to lung cancer risk: a multiomics data integration study.Translational lung cancer research · 2025Article
- Therapeutic potential of tumor-associated neutrophils: dual role and phenotypic plasticity.Signal transduction and targeted therapy · 2025Review
- Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictive biomarkers for treatment response in primary advanced hypopharyngeal squamous cell carcinoma treated with chemoimmunotherapy.Clinical and experimental medicine · 2025Article
- Large vesicles from ageing neutrophils: novel safeguards for the resolution of inflammation.Signal transduction and targeted therapy · 2025Article
- Review
- Tumor‑associated neutrophils: Critical regulators in cancer progression and therapeutic resistance (Review).International journal of oncology · 2025Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Elevated peripheral blood and tumor-infiltrating neutrophils are often associated with a poor patient prognosis. However, therapeutic strategies to target these cells are difficult to implement due to the life-threatening risk of neutropenia. In a genetically engineered mouse model of lung adenocarcinoma, tumor-associated neutrophils (TAN) demonstrate tumor-supportive capacities and have a prolonged lifespan compared to circulating neutrophils. Here, we show that tumor cell-derived GM-CSF triggers the expression of the anti-apoptotic Bcl-xL protein and enhances neutrophil survival through JAK/STAT signaling. Targeting Bcl-xL activity with a specific BH3 mimetic, A-1331852, blocked the induced neutrophil survival without impacting their normal lifespan. Specifically, oral administration with A-1331852 decreased TAN survival and abundance, and reduced tumor growth without causing neutropenia. We also show that G-CSF, a drug used to combat neutropenia in patients receiving chemotherapy, increased the proportion of young TANs and augmented the anti-tumor effect resulting from Bcl-xL blockade. Finally, our human tumor data indicate the same role for Bcl-xL on pro-tumoral neutrophil survival. These results altogether provide preclinical evidence for safe neutrophil targeting based on their aberrant intra-tumor longevity.
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Registered trials
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 OpenQuestion graph.