ArticleOncoimmunology
Inhibition of RON kinase potentiates anti-CTLA-4 immunotherapy to shrink breast tumors and prevent metastatic outgrowth.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Loss of short-form Ron promotes B and T cell cooperation to prevent outgrowth of breast cancer bone metastasis.bioRxiv : the preprint server for biology · 2026Article
- Medicinal Chemistry of Small-Molecule c-Met Inhibitors: From Approved Therapies to Emerging Multitarget Anticancer Agents.International journal of molecular sciences · 2026Review
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Review
- Decoding breast cancer treatment resistance through genetic, epigenetic, and immune-regulatory mechanisms: from molecular insights to translational perspectives.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- The cellular composition of the tumor microenvironment is an important marker for predicting therapeutic efficacy in breast cancer.Frontiers in immunology · 2024Review
- Targeting isoforms of RON kinase (MST1R) drives antitumor efficacy.Cell death and differentiation · 2023Article
- Review
- Tailoring therapies to counter the divergent immune landscapes of breast cancer.Frontiers in cell and developmental biology · 2023Review
- The role of tumor microenvironment in drug resistance: emerging technologies to unravel breast cancer heterogeneity.Frontiers in oncology · 2023Review
- Single-cell RNA sequencing reveals localized tumour ablation and intratumoural immunostimulant delivery potentiate T cell mediated tumour killing.Clinical and translational medicine · 2022Article
- Blocking Short-Form Ron Eliminates Breast Cancer Metastases through Accumulation of Stem-Like CD4+ T Cells That Subvert Immunosuppression.Cancer discovery · 2021Article
- Tumor-Associated Macrophages: Critical Players in Drug Resistance of Breast Cancer.Frontiers in immunology · 2021Review
- Insights from transgenic mouse models of PyMT-induced breast cancer: recapitulating human breast cancer progression in vivo.Oncogene · 2021Review
- A DNA Hypomethylating Drug Alters the Tumor Microenvironment and Improves the Effectiveness of Immune Checkpoint Inhibitors in a Mouse Model of Pancreatic Cancer.Cancer research · 2020Article
- The MSP-RON axis stimulates cancer cell growth in models of triple negative breast cancer.Molecular oncology · 2020Article
- MSP-RON Pathway: Potential Regulator of Inflammation and Innate Immunity.Frontiers in immunology · 2020Review
- Mapping actionable pathways and mutations in brain tumours using targeted RNA next generation sequencing.Acta neuropathologica communications · 2019Article
- Therapeutic efficacy, pharmacokinetic profiles, and toxicological activities of humanized antibody-drug conjugate Zt/g4-MMAE targeting RON receptor tyrosine kinase for cancer therapy.Journal for immunotherapy of cancer · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The advent of immune checkpoint blockade as a new strategy for immunotherapy has changed the outlook for many aggressive cancers. Although complete tumor eradication is attainable in some cases, durable clinical responses are observed only in a small fraction of patients, underlining urgent need for improvement. We previously showed that RON, a receptor tyrosine kinase expressed in macrophages, suppresses antitumor immune responses, and facilitates progression and metastasis of breast cancer. Here, we investigated the molecular changes that occur downstream of RON activation in macrophages, and whether inhibition of RON can cooperate with checkpoint immunotherapy to eradicate tumors. Activation of RON by its ligand, MSP, altered the gene expression profile of macrophages drastically and upregulated surface levels of CD80 and PD-L1, ligands for T-cell checkpoint receptors CTLA-4 and PD-1. Genetic deletion or pharmacological inhibition of RON in combination with anti-CTLA-4, but not with anti-PD-1, resulted in improved clinical responses against orthotopically transplanted tumors compared to single-agent treatment groups, resulting in complete tumor eradication in 46% of the animals. Positive responses to therapy were associated with higher levels of T-cell activation markers and tumor-infiltrating lymphocytes. Importantly, co-inhibition of RON and anti-CTLA-4 was also effective in clearing metastatic breast cancer cells in lungs, resulting in clinical responses in nearly 60% of the mice. These findings suggest that RON inhibition can be a novel approach to potentiate responses to checkpoint immunotherapy in breast cancer.
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