ArticleThe Journal of clinical investigation2018
Tumor-secreted Pros1 inhibits macrophage M1 polarization to reduce antitumor immune response.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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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
112 citing papers in PubMed, 211 citations in OpenAlex.
- Structural basis of phosphatidylserine enhancement of Gas6 ligand-induced Axl activation.bioRxiv : the preprint server for biology · 2026Article
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- Single-Cell Atlas of Renal Cell Carcinoma Brain Metastasis Uncovers Mechanisms of Immune Dysfunction and Resistance.bioRxiv : the preprint server for biology · 2026Article
- Multi-omics integration identifies APOE as a metabolic regulator of macrophage-fibroblast crosstalk in idiopathic pulmonary fibrosis.Frontiers in immunology · 2026Article
- Uncovering cellular perturbations and key mediator communications in liver cancer using single-cell RNA sequencing.Frontiers in immunology · 2026Article
- Multi-omics Approaches to CCAAT/Enhancer-Binding Protein Beta in Oral Squamous Cell Carcinoma: Crosstalk Between Tumor Cells and Tumor-Associated Macrophages Driving Disease Progression.Current cancer drug targets · 2026Article
- Systemic exosome abundance and comprehensive proteome profile of lymphoma-derived exosomes: Insights into host-tumor interactions.Medical oncology (Northwood, London, England) · 2025Article
- Proteolytic profiling of human plasma reveals an immunoactive complement C3 fragment.The EMBO journal · 2025Article
- From pathogenesis to therapeutic targeting: new insight into TAM receptors in rheumatoid arthritis.Cell & bioscience · 2025Review
- PROS1-MERTK Axis Drives Tumor Microenvironment Crosstalk and Progression in Papillary Thyroid Microcarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- FMRP silencing via siRNA lipid nanoparticles to reprogram the tumor microenvironment and enhance anti-PD-1 efficacy in triple-negative breast cancer.Materials today. Bio · 2025Article
- Exploiting structural variability in the kinase back-pocket to modulate polypharmacology of TAM inhibitors.European journal of medicinal chemistry · 2025Article
- A Computational Approach to Characterize the Protein S-Mer Tyrosine Kinase (PROS1-MERTK) Protein-Protein Interaction Dynamics.Cell biochemistry and biophysics · 2025Article
- Global research trends in tumor-associated macrophage studies: a bibliometric analysis.Discover oncology · 2025Article
- PTP Inhibition Improves the Macrophage Antitumor Immune Response and the Efficacy of Chemo- and Radiotherapy.Cancer immunology research · 2025Article
- Discovery of Novel TYRO3/MERTK Dual Inhibitors.Journal of medicinal chemistry · 2025Article
- Different inflammatory, fibrotic, and immunological signatures between pre-fibrotic and overt primary myelofibrosis.Haematologica · 2025Article
- Harnessing myeloid cells in cancer.Molecular cancer · 2025Review
- Proteolysis of TAM receptors in autoimmune diseases and cancer: what does it say to us?Cell death & disease · 2025Review
- In silico research of coagulation- and fibrinolysis-related genes for predicting prognosis of clear cell renal cell carcinoma.Translational andrology and urology · 2025Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tyro3, Axl, Mer (TAM) receptor tyrosine kinases reduce inflammatory, innate immune responses. We demonstrate that tumor-secreted protein S (Pros1), a Mer/Tyro3 ligand, decreased macrophage M1 cytokine expression in vitro and in vivo. In contrast, tumor cells with CRISPR-based deletion of Pros1 failed to inhibit M1 polarization. Tumor cell-associated Pros1 action was abrogated in macrophages from Mer- and Tyro3- but not Axl-KO mice. In addition, several other murine and human tumor cell lines suppressed macrophage M1 cytokine expression induced by IFN-γ and LPS. Investigation of the suppressive pathway demonstrated a role for PTP1b complexing with Mer. Substantiating the role of PTP1b, M1 cytokine suppression was also lost in macrophages from PTP1b-KO mice. Mice bearing Pros1-deficient tumors showed increased innate and adaptive immune infiltration, as well as increased median survival. TAM activation can also inhibit TLR-mediated M1 polarization. Treatment with resiquimod, a TLR7/8 agonist, did not improve survival in mice bearing Pros1-secreting tumors but doubled survival for Pros1-deleted tumors. The tumor-derived Pros1 immune suppressive system, like PD-L1, was cytokine responsive, with IFN-γ inducing Pros1 transcription and secretion. Inhibition of Pros1/TAM interaction represents a potential novel strategy to block tumor-derived immune suppression.
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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.