ArticlePloS one2018
MMP-9 inhibition promotes anti-tumor immunity through disruption of biochemical and physical barriers to T-cell trafficking to tumors.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 103 citations in OpenAlex.
- Randomized, open-label, phase 2 study of andecaliximab plus nivolumab versus nivolumab alone in advanced gastric cancer identifies biomarkers associated with survival.Journal for immunotherapy of cancer · 2021Trial
- Therapeutic potential of inhibitors of gelatinases MMP-2 and MMP-9 for the treatment of breast cancer.The FEBS journal · 2026Review
- Targeting the hsa-miR-155-5p-BACH1-MMP-9 Signaling Hub in Lung Cancer: A Novel Anticancer Mechanism of Thymoquinone.Biomolecules · 2026Article
- Immunocyte senescence: A new perspective on the remodeling of the ovarian cancer microenvironment and therapeutic intervention.Journal of pharmaceutical analysis · 2026Review
- MMP9 Genotype and Systemic T-Cell Subsets Correlate With Structural and Functional Outcomes in Neovascular Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2026Article
- Fusobacterium nucleatum in cancer: Interactions with microbiota, tumour colonisation and cancer progression.Clinical and translational medicine · 2026Review
- Oncometabolites and Hypoxia-Regulated Exosomes Shape HIF-Driven Macrophage Programs Across Type 2 Diabetes, Atherosclerosis, and Cancer.International journal of molecular sciences · 2026Review
- Targeting Matrix Stiffness and Mechanotransduction in Breast Cancer: Implications for Emerging Therapies.International journal of molecular sciences · 2026Review
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- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- Harnessing cellular immunotherapy for cholangiocarcinoma: an integrated roadmap for overcoming resistance.Frontiers in immunology · 2026Review
- Targeting Tumor-Associated Macrophages to Reshape the Immuno-Mechanical Landscape: Molecular Mechanisms and Therapeutic Strategies.International journal of biological sciences · 2026Review
- Multi-omics reveals the immune and metabolic characteristics and associations in non-mucinous ovarian cancer.Journal of ovarian research · 2025Article
- Self-assembly of hybrid 3D cultures by integrating living and synthetic cells.Nature communications · 2025Article
- Ligand-receptor interaction profiling as a predictive biomarker for anti-PD-1 therapy response in melanoma.Clinical and experimental medicine · 2025Article
- Collagen in pituitary adenomas: A comprehensive review of biological roles and clinical implications.Journal of clinical & translational endocrinology · 2025Review
- Mimicking Gastric Cancer Collagen Reorganization with Decellularized ECM-Based Scaffolds.Biology · 2025Review
- Inside a Metastatic Fracture: Molecular Bases and New Potential Therapeutic Targets.Cancer medicine · 2025Review
- The Potential Use of Digital Twin Technology for Advancing CAR-T Cell Therapy.Current issues in molecular biology · 2025Review
- Immunogenic shift of arginine metabolism triggers systemic metabolic and immunological reprogramming to suppress HER2 + breast cancer.Cancer & metabolism · 2025Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matrix metalloproteinase-9 (MMP-9), whose expression is frequently dysregulated in cancer, promotes tumor growth, invasion, and metastasis by multiple mechanisms, including extracellular matrix remodeling and growth-factor and cytokine activation. We developed a monoclonal antibody against murine MMP-9, which we found decreased growth of established primary tumors in an orthotopic model of HER2-driven breast cancer (HC11-NeuT) in immunocompetent mice. RNA sequencing (RNAseq) profiling of NeuT tumors and additional mouse model tumors revealed that anti-MMP-9 treatment resulted in upregulation of immune signature pathways associated with cytotoxic T-cell response. As there is a need to boost the low response rates observed with anti-PDL1 antibody treatment in the clinical setting, we assessed the potential of anti-MMP-9 to improve T-cell response to immune checkpoint inhibitor anti-PDL1 in NeuT tumors. Anti-MMP-9 and anti-PDL1 cotreatment reduced T-cell receptor (TCR) clonality and increased TCR diversity, as detected by TCR sequencing of NeuT tumors. Flow cytometry analyses of tumors showed that the combination treatment increased the frequency of CD3+ T cells, including memory/effector CD4 and CD8 T cells, but not regulatory T cells, among tumor-infiltrating leukocytes. Moreover, in vitro enzymatic assays corroborated that MMP-9 cleaves key T-cell chemoattractant CXC receptor 3 ligands (CXC ligand [CXCL] 9, CXCL10, and CXCL11) and renders them inactive in T-cell migration assays. Consistent with our in vitro experiments, analysis of NeuT tumor protein lysates showed that anti-MMP-9 treatment increases expression of CXCL10 and other T cell-stimulating factors, such as interleukin (IL)-12p70 and IL-18. We show that inhibition of MMP-9, a key component of the tumor-promoting and immune-suppressive myeloid inflammatory milieu, increases T-helper cell 1 type cytokines, trafficking of effector/memory T cells into tumors, and intratumoral T-cell diversity.
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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.