ArticleGenome medicine2020
Small-molecule MMP2/MMP9 inhibitor SB-3CT modulates tumor immune surveillance by regulating PD-L1.
Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 154 citations in OpenAlex.
- Autophagy Orchestrates Anti-Tumor Immunity to Enhance Chemosensitivity via the FBXW2/C/EBPβ/TIMP-2 Axis in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A guide to the types, structures, and multifaceted functions of matrix metalloproteinases in cancer.The FEBS journal · 2026Review
- Therapeutic potential of inhibitors of gelatinases MMP-2 and MMP-9 for the treatment of breast cancer.The FEBS journal · 2026Review
- Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
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- Propranolol improves cognitive function and glymphatic system recovery through STAT3/MMP2 pathway after TBI.PloS one · 2026Article
- Matrix Metalloproteinase Inhibition in Melanoma.Experimental dermatology · 2026Review
- Ferroptosis meets cancer immunotherapy: Overcoming the crosstalk challenges through advanced drug delivery strategies.Acta pharmaceutica Sinica. B · 2025Review
- Prognostic Significance of the Comprehensive Biomarker Analysis in Colorectal Cancer.Life (Basel, Switzerland) · 2025Review
- Paracrine signaling in cancer-associated fibroblasts: central regulators of the tumor immune microenvironment.Journal of translational medicine · 2025Review
- Investigating the Genetic Links Between Immune Cell Profiles and Bladder Cancer: A Multidisciplinary Bioinformatics Approach.Biomedicines · 2025Article
- Advances in cancer immunotherapy: historical perspectives, current developments, and future directions.Molecular cancer · 2025Review
- Matrix Metalloproteinases in Glioma: Drivers of Invasion and Therapeutic Targets.Biotech (Basel (Switzerland)) · 2025Review
- Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer.Experimental hematology & oncology · 2025Review
- Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis.Scientific reports · 2025Article
- Article
- Extracellular Matrix as a Target in Melanoma Therapy: From Hypothesis to Clinical Trials.Cells · 2024Review
- Identifying compound-protein interactions with knowledge graph embedding of perturbation transcriptomics.Cell genomics · 2024Article
- Mediator complex subunit 1 promotes oral squamous cell carcinoma progression by activating MMP9 transcription and suppressing CD8Journal of experimental & clinical cancer research : CR · 2024Article
- Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway.BMC cardiovascular disorders · 2024Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint blockade (ICB) therapy has demonstrated considerable clinical benefit in several malignancies, but has shown favorable response in only a small proportion of cancer patients. Recent studies have shown that matrix metalloproteinases (MMPs) are highly associated with the microenvironment of tumors and immune cells. However, it is unknown whether MMPs are involved in immunotherapy.
methodsHere, we used integrative analysis to explore the expression landscape of the MMP family and its association with immune features across multiple cancer types. We used T cell cytotoxicity-mediated tumor killing assay to determine the co-cultured T cell activity of SB-3CT, an MMP2/9 inhibitor. We then used in vitro assays to examine the regulating roles of SB-3CT on PD-L1. We further characterized the efficacy of SB-3CT, in combination with anti-PD-1 and/or anti-CTLA4 treatment in mouse models with melanoma and lung cancer.
resultsOur computational analysis demonstrated a strong association between MMP2/9 and immune features. We demonstrated that inhibition of MMP2/9 by SB-3CT significantly reduced the tumor burden and improved survival time by promoting anti-tumor immunity. Mechanistically, we showed that SB-3CT treatment significantly diminished both mRNA and protein levels of PD-L1 in cancer cells. Pre-clinically, SB-3CT treatment enhanced the therapeutic efficacy of PD-1 or CTLA-4 blockade in the treatment of both primary and metastatic tumors.
conclusionsOur study unraveled novel molecular mechanisms regarding the regulation of tumor PD-L1 and provided a novel combination therapeutic strategy of SB-3CT and ICB therapy to enhance the efficacy of immunotherapy.
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