ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Stabilizing Tumor-Resident Mast Cells Restores T-Cell Infiltration and Sensitizes Sarcomas to PD-L1 Inhibition.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 33 citations in OpenAlex.
- Monocyte-lineage tumor infiltration predicts immunoradiotherapy response in advanced pretreated soft-tissue sarcoma: phase 2 trial results.Signal transduction and targeted therapy · 2025Trial
- Targeting histamine signaling: repurposing antihistamines for cancer chemotherapy and immunotherapy.Archives of pharmacal research · 2026Review
- Mechanistic modeling of tumor immune microenvironment reveals strategies to enhance antibody-drug conjugates' efficacy.Journal for immunotherapy of cancer · 2026Article
- Mast Cells in the Developing Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- A multiphysics computational model of focused ultrasound-enhanced drug delivery using temperature-sensitive liposomes.Biomechanics and modeling in mechanobiology · 2026Article
- Mast cell specific Cyp11a1 deficiency promotes T cell mediated immunity and suppresses tumour metastasis in a mouse model of melanoma.Scientific reports · 2026Article
- Spatial transcriptomic mapping of canine osteosarcoma reveals immune microenvironment features linked to survival.Communications biology · 2026Article
- AllergoOncology in Review: Harnessing Allergy in the Field of Oncology to Improve Patient Outcomes.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Review
- <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>.Oncology reports · 2026Review
- Modulating tumor mechanics and vascular barriers to enhance chemotherapy efficacy in pancreatic tumors and melanoma.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Enhancing nanomedicine efficacy in KPC pancreatic tumors through ketotifen-mediated tumor microenvironment remodeling.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Research progress on tumor extracellular matrix stiffness and immunosuppression.Frontiers in immunology · 2026Review
- Is there a link between fascia and cancer? From potential mechanisms to future treatment options.Frontiers in physiology · 2026Review
- Tumor-Infiltrating Mast Cells Enhance Neoadjuvant Therapy Efficacy in ESCC via Modulation of the Desmoplastic Microenvironment.OncoTargets and therapy · 2026Article
- Retinoic Acid Reprograms Mast Cells Toward a Proinflammatory State to Enhance Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Deciphering the Role of Mast Cells in HPV-Related Cancers.International journal of molecular sciences · 2025Review
- Review
- Physiologically based pharmacokinetic model for CAR-T cell delivery and efficacy in solid tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Soil and Seed: Tumor Microenvironment Nurtures Immunotherapy Resistance and Renewal.International journal of molecular sciences · 2025Review
- Optimizing therapeutic outcomes with Mechanotherapy and Ultrasound Sonopermeation in solid tumors.PLoS computational biology · 2025Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeTo explore the cellular cross-talk of tumor-resident mast cells (MC) in controlling the activity of cancer-associated fibroblasts (CAF) to overcome tumor microenvironment (TME) abnormalities, enhancing the efficacy of immune-checkpoint inhibitors in sarcoma. EXPERIMENTAL
designWe used a coculture system followed by further validation in mouse models of fibrosarcoma and osteosarcoma with or without administration of the MC stabilizer and antihistamine ketotifen. To evaluate the contribution of ketotifen in sensitizing tumors to therapy, we performed combination studies with doxorubicin chemotherapy and anti-PD-L1 (B7-H1, clone 10F.9G2) treatment. We investigated the ability of ketotifen to modulate the TME in human sarcomas in the context of a repurposed phase II clinical trial.
resultsInhibition of MC activation with ketotifen successfully suppressed CAF proliferation and stiffness of the extracellular matrix accompanied by an increase in vessel perfusion in fibrosarcoma and osteosarcoma as indicated by ultrasound shear wave elastography imaging. The improved tissue oxygenation increased the efficacy of chemoimmunotherapy, supported by enhanced T-cell infiltration and acquisition of tumor antigen-specific memory. Importantly, the effect of ketotifen in reducing tumor stiffness was further validated in sarcoma patients, highlighting its translational potential.
conclusionsOur study suggests the targeting of MCs with clinically administered drugs, such as antihistamines, as a promising approach to overcome resistance to immunotherapy in sarcomas.
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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 Socratic graph.