ArticleJCI insight2018
MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- A MERTK-Targeting Antibody-Drug Conjugate Selectively Depletes M2 Tumor-Associated Macrophages and MERTK-Expressing Cancer Cells.Cancer research · 2026Article
- Suppression of cardiac allograft vasculopathy by a macrophage efferocytosis receptor.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Decoding macrophage heterogeneity in the pulmonary fibrosis lung cancer transition.Frontiers in immunology · 2026Review
- MERTK inhibition improves therapeutic efficacy of immune checkpoint inhibitors in hepatocellular carcinoma.Oncoimmunology · 2025Article
- Discovery of Novel 2-Substituted Aniline Pyrimidine Based Derivatives as Potent Mer/c-Met Dual Inhibitors with Improvement Bioavailability.Biomolecules · 2025Article
- Navigating TAM receptor dynamics in tumour immunotherapy.Cancer immunology, immunotherapy : CII · 2025Review
- Proteolysis of TAM receptors in autoimmune diseases and cancer: what does it say to us?Cell death & disease · 2025Review
- T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives.Frontiers in immunology · 2025Review
- Phosphatidylserine externalization as immune checkpoint in cancer.Pflugers Archiv : European journal of physiology · 2024Review
- MERTK inhibition selectively activates a DC - T-cell axis to provide anti-leukemia immunity.Leukemia · 2024Article
- MerTK Induces Dysfunctional Dendritic Cells by Metabolic Reprogramming.Cancer immunology research · 2024Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- Article
- MERTK Inhibition as a Targeted Novel Cancer Therapy.International journal of molecular sciences · 2024Review
- Therapeutic targeting of the functionally elusive TAM receptor family.Nature reviews. Drug discovery · 2024Review
- Novel Substrate Prediction for the TAM Family of RTKs Using Phosphoproteomics and Structure-Based Modeling.ACS chemical biology · 2024Article
- Design, Synthesis, and Biological Evaluation of 2-Substituted Aniline Pyrimidine Derivatives as Potent Dual Mer/c-Met Inhibitors.Molecules (Basel, Switzerland) · 2024Article
- TAM family kinases as therapeutic targets at the interface of cancer and immunity.Nature reviews. Clinical oncology · 2023Review
- A Real-Time Image-Based Efferocytosis Assay for the Discovery of Functionally Inhibitory Anti-MerTK Antibodies.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Inhibiting efferocytosis reverses macrophage-mediated immunosuppression in the leukemia microenvironment.Frontiers in immunology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
MERTK is ectopically expressed and promotes survival in acute lymphoblastic leukemia (ALL) cells and is thus a potential therapeutic target. Here we demonstrate both direct therapeutic effects of MERTK inhibition on leukemia cells and induction of anti-leukemia immunity via suppression of the coinhibitory PD-1 axis. A MERTK-selective tyrosine kinase inhibitor, MRX-2843, mediated therapeutic anti-leukemia effects in immunocompromised mice bearing a MERTK-expressing human leukemia xenograft. In addition, inhibition of host MERTK by genetic deletion (Mertk-/- mice) or treatment with MRX-2843 significantly decreased tumor burden and prolonged survival in immune-competent mice inoculated with a MERTK-negative ALL, suggesting immune-mediated therapeutic activity. In this context, MERTK inhibition led to significant decreases in expression of the coinhibitory ligands PD-L1 and PD-L2 on CD11b+ monocytes/macrophages in the leukemia microenvironment. Furthermore, although T cells do not express MERTK, inhibition of MERTK indirectly decreased PD-1 expression on CD4+ and CD8+ T cells and decreased the incidence of splenic FOXP3+ Tregs at sites of leukemic infiltration, leading to increased T cell activation. These data demonstrate direct and immune-mediated therapeutic activities in response to MERTK inhibition in ALL models and provide validation of a translational agent targeting MERTK for modulation of tumor immunity.
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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.