ArticleCancer research2021
Axl and Mertk Receptors Cooperate to Promote Breast Cancer Progression by Combined Oncogenic Signaling and Evasion of Host Antitumor Immunity.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed.
- Single-Cell RNA-Sequencing Reveals Tumor Microenvironment Composition and Prior Therapy Modulate Response to Axl Inhibition.Cellular and molecular bioengineering · 2026Article
- MerTK Is Regulated by Orphan Nuclear Receptor 4A1 (NR4A1) and NR4A2 in Colon Cancer Cells.Cancers · 2026Article
- A MERTK-Targeting Antibody-Drug Conjugate Selectively Depletes M2 Tumor-Associated Macrophages and MERTK-Expressing Cancer Cells.Cancer research · 2026Article
- A systems approach identifies MERTK as a therapeutic vulnerability in ZFTA-RELA-driven ependymomas.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- [Role of Receptor Tyrosine Kinase AXL in Cancer Targeted Therapy Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Preclinical evaluation of CPL423: a novel potent small-molecule inhibitor of TAM family and FLT3 kinase for cancer therapy.Frontiers in pharmacology · 2026Article
- Phospholipid scramblases TMEM16F and Xkr8 mediate distinct features of phosphatidylserine (PS) externalization and immune suppression to promote tumor growth.Cell death discovery · 2025Article
- STK38 Kinase Promotes Cell Migration Induced by Oncogenic Ras via MerTK Activation.International journal of molecular sciences · 2025Article
- Engineering Efferocytosis for Bone Regeneration.Macromolecular bioscience · 2025Review
- Discovery of Novel 2-Substituted Aniline Pyrimidine Based Derivatives as Potent Mer/c-Met Dual Inhibitors with Improvement Bioavailability.Biomolecules · 2025Article
- ALOX15B-based efferocytosis clusters: prognostic implications and immune cell infiltration in breast cancer.Discover oncology · 2025Article
- Navigating TAM receptor dynamics in tumour immunotherapy.Cancer immunology, immunotherapy : CII · 2025Review
- Axl Regulation of NK Cell Activity Creates an Immunosuppressive Tumor Immune Microenvironment in Head and Neck Cancer.Cancers · 2025Article
- Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer.Cell communication and signaling : CCS · 2025Review
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Expression, purification and characterization of phosphatidylserine-targeting antibodies for biochemical and therapeutic applications.Methods in cell biology · 2025Article
- Establishing Tyro3, Axl, and Mertk Chinese hamster ovary (CHO) reporter cell lines for cancer immunology and therapeutic applications.Methods in cell biology · 2025Article
- Axl inhibitor-mediated reprogramming of the myeloid compartment of theFrontiers in immunology · 2025Article
- STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Sensitive Genes for Cervical Cancer: Two-Sample Mendelian Randomization with Experimental Validation.International journal of women's health · 2025Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors.
Funding
Abstract
Despite the promising clinical benefit of targeted and immune checkpoint blocking therapeutics, current strategies have limited success in breast cancer, indicating that additional inhibitory pathways are required to complement existing therapeutics. TAM receptors (Tyro-3, Axl, and Mertk) are often correlated with poor prognosis because of their capacities to sustain an immunosuppressive environment. Here, we ablate Axl on tumor cells using CRISPR/Cas9 gene editing, and by targeting Mertk in the tumor microenvironment (TME), we observed distinct functions of TAM as oncogenic kinases, as well as inhibitory immune receptors. Depletion of Axl suppressed cell intrinsic oncogenic properties, decreased tumor growth, reduced the incidence of lung metastasis and increased overall survival of mice when injected into mammary fat pad of syngeneic mice, and demonstrated synergy when combined with anti-PD-1 therapy. Blockade of Mertk function on macrophages decreased efferocytosis, altered the cytokine milieu, and resulted in suppressed macrophage gene expression patterns. Mertk-knockout mice or treatment with anti-Mertk-neutralizing mAb also altered the cellular immune profile, resulting in a more inflamed tumor environment with enhanced T-cell infiltration into tumors and T-cell-mediated cytotoxicity. The antitumor activity from Mertk inhibition was abrogated by depletion of cytotoxic CD8α T cells by using anti-CD8α mAb or by transplantation of tumor cells into B6.CB17-Prkdc SCID mice. Our data indicate that targeting Axl expressed on tumor cells and Mertk in the TME is predicted to have a combinatorial benefit to enhance current immunotherapies and that Axl and Mertk have distinct functional activities that impair host antitumor response. SIGNIFICANCE: This study demonstrates how TAM receptors act both as oncogenic tyrosine kinases and as receptors that mediate immune evasion in cancer progression.
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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.