ArticleJournal for immunotherapy of cancer2018
Non-invasive biomarkers derived from the extracellular matrix associate with response to immune checkpoint blockade (anti-CTLA-4) in metastatic melanoma patients.
Article in Journal for immunotherapy of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature.Frontiers in immunology · 2023Pooled it
- Degradation fragments of Tau and type IV collagen as serum biomarkers in patients with recurrent glioblastoma treated with nivolumab and bevacizumab.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Trial
- Blood-based extracellular matrix biomarkers as predictors of survival in patients with metastatic pancreatic ductal adenocarcinoma receiving pegvorhyaluronidase alfa.Journal of translational medicine · 2021Trial
- Collagen fragments quantified in serum as measures of desmoplasia associate with survival outcome in patients with advanced pancreatic cancer.Scientific reports · 2019Trial
- Failed immune responses across multiple pathologies share pan-tumor and circulating lymphocytic targets.The Journal of clinical investigation · 2019Trial
- Mechanobiology of the tumor microenvironment: a review of therapeutic interactions and in vitro elasticity measurement techniques.Journal of biomedical science · 2026Review
- Collagen-derived biomarkers reveal distinct fibrotic responses among cancer-associated fibroblasts.Scientific reports · 2026Article
- Article
- Inhibiting the Secreted RGDKGE Collagen Peptide Selectively Controls CD8The American journal of pathology · 2026Article
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- Circulating EMID2 as a Prognostic Biomarker of Poor Outcomes in Patients with Metastatic Colorectal Cancer.Biomarker insights · 2026Article
- Serum levels of the C-terminal pro-peptide of type V collagen have prognostic potential and are associated with a normal subtype of desmoplasia in a retrospective cohort of patients with esophagogastric cancer.Therapeutic advances in medical oncology · 2026Article
- Cost-effective Mueller matrix microscopy for label-free differentiation of melanoma from normal skin and common skin cancer types.Biomedical optics express · 2025Article
- BIGH3 is a mediator of TGFβ-Induced collagen formation in fibrosis and pancreatic cancer and a potential therapeutic target.Scientific reports · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Targeting collagen to optimize cancer immunotherapy.Experimental hematology & oncology · 2025Review
- Micron-Sized FeBioengineering (Basel, Switzerland) · 2025Article
- Targeting Matrix Metalloproteinases and Their Inhibitors in Melanoma.International journal of molecular sciences · 2024Review
- HSP90AA1 is an unfavorable prognostic factor for hepatocellular carcinoma and contributes to tumorigenesis and chemotherapy resistance.Translational oncology · 2024Article
- Mechanisms of assembly and remodelling of the extracellular matrix.Nature reviews. Molecular cell biology · 2024Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExcessive extracellular matrix (ECM) remodeling and a reactive stroma can affect T-cell infiltration and T-cell activity in the tumor and hereby influence response to immune checkpoint inhibitors (ICI). In the pursuit of finding biomarkers that predict treatment response, we evaluated the association between serum biomarkers of collagen and vimentin turnover and outcomes in metastatic melanoma patients treated with the anti-CTLA-4 antibody ipilimumab (IPI).
methodsType III collagen formation (PRO-C3), MMP-degraded type I, type III and type IV collagens (C1M, C3M and C4M), and citrullinated and MMP-degraded vimentin (VICM) were measured with ELISAs in serum from metastatic melanoma patients before (n = 66) and 3 weeks after (n = 52) initiation of IPI treatment. Biomarker levels were associated with Disease Control Rate (DCR) and survival outcomes.
resultsWe found that baseline levels of PRO-C3 (p = 0.011), C1M (p = 0.003), C3M (p = 0.013) and C4M (p = 0.027) were significantly elevated in patients with progressive disease (PD). Univariate Cox regression analysis identified high PRO-C3 (p = 0.021) and C4M (p = 0.008) as predictors of poor overall survival (OS) and the biomarkers remained significant when evaluated with other covariates (PRO-C3 (p = 0.049) and C4M (p = 0.046)). Multivariate analysis identified VICM as a predictor of longer OS (p = 0.026). Similarly, a high C3M/PRO-C3 ratio predicted for increased OS (p = 0.034). Only C3M (p = 0.003) and VICM (p < 0.0001) increased 3 weeks after treatment.
conclusionsECM and tissue remodeling quantified in pre-treatment serum were associated with response and survival outcomes in metastatic melanoma patients treated with IPI. This highlights the importance of addressing the ECM and stromal component non-invasively in future ICI studies.
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