ArticleCancer discovery2021
AXL Inhibition in Macrophages Stimulates Host-versus-Leukemia Immunity and Eradicates Naïve and Treatment-Resistant Leukemia.
Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 49 citations in OpenAlex.
- Sitravatinib plus tislelizumab in locally recurrent or metastatic triple-negative breast cancer: a multi-cohort, single-arm, phase II clinical trial (SPARK Trial).Molecular cancer · 2025Trial
- Bemcentinib as monotherapy and in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy: a phase 1b/2a trial.Nature communications · 2025Trial
- Trial
- Single-Cell RNA-Sequencing Reveals Tumor Microenvironment Composition and Prior Therapy Modulate Response to Axl Inhibition.Cellular and molecular bioengineering · 2026Article
- FADS1-mediated Efferocytosis in Tumor-Associated Macrophages Shapes an Immunosuppressive Microenvironment in Gastric Cancer.Cellular and molecular life sciences : CMLS · 2026Article
- Preclinical evaluation of CPL423: a novel potent small-molecule inhibitor of TAM family and FLT3 kinase for cancer therapy.Frontiers in pharmacology · 2026Article
- Review
- Tyro3 deletion is protective in experimental autoimmune encephalomyelitis.Immunology and cell biology · 2025Article
- Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer.Nature immunology · 2025Article
- Untangling the loops ofLeukemia & lymphoma · 2025Review
- New insights into combined immunotherapy for hepatocellular carcinoma associated with liver cirrhosis.Frontiers in immunology · 2025Review
- Enhancing natural killer cell anti-tumour activity through macrophage manipulation.Frontiers in immunology · 2025Review
- Axl inhibitor-mediated reprogramming of the myeloid compartment of theFrontiers in immunology · 2025Article
- AXL in myeloid malignancies - an elusive target?Biomarker research · 2024Article
- MERTK inhibition selectively activates a DC - T-cell axis to provide anti-leukemia immunity.Leukemia · 2024Article
- Phosphatidylserine externalization as immune checkpoint in cancer.Pflugers Archiv : European journal of physiology · 2024Review
- AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.Experimental hematology & oncology · 2024Review
- MERTK Inhibition as a Targeted Novel Cancer Therapy.International journal of molecular sciences · 2024Review
- Triterpenoids-templated self-assembly nanosystem for biomimetic delivery of CRISPR/Cas9 based on the synergy of TLR-2 and ICB to enhance HCC immunotherapy.Acta pharmaceutica Sinica. B · 2024Article
- Evaluation of the Role of AXL in Fusion-positive Pediatric Rhabdomyosarcoma Identifies the Small-molecule Inhibitor Bemcentinib (BGB324) as Potent Chemosensitizer.Molecular cancer therapeutics · 2024Article
Corrections and comments
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Authors and funding
37 authors at 11 institutions in 3 countries.
Funding
Abstract
Acute leukemias are systemic malignancies associated with a dire outcome. Because of low immunogenicity, leukemias display a remarkable ability to evade immune control and are often resistant to checkpoint blockade. Here, we discover that leukemia cells actively establish a suppressive environment to prevent immune attacks by co-opting a signaling axis that skews macrophages toward a tumor-promoting tissue repair phenotype, namely the GAS6/AXL axis. Using aggressive leukemia models, we demonstrate that ablation of the AXL receptor specifically in macrophages, or its ligand GAS6 in the environment, stimulates antileukemic immunity and elicits effective and lasting natural killer cell- and T cell-dependent immune response against naïve and treatment-resistant leukemia. Remarkably, AXL deficiency in macrophages also enables PD-1 checkpoint blockade in PD-1-refractory leukemias. Finally, we provide proof-of-concept that a clinical-grade AXL inhibitor can be used in combination with standard-of-care therapy to cure established leukemia, regardless of AXL expression in malignant cells. SIGNIFICANCE: Alternatively primed myeloid cells predict negative outcome in leukemia. By demonstrating that leukemia cells actively evade immune control by engaging AXL receptor tyrosine kinase in macrophages and promoting their alternative priming, we identified a target which blockade, using a clinical-grade inhibitor, is vital to unleashing the therapeutic potential of myeloid-centered immunotherapy.
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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.