Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Non-invasive biomarkers derived from the extracellular matrix associate with response to immune checkpoint blockade (anti-CTLA-4) in metastatic melanoma patients

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Targetless T cells in cancer immunotherapy

    Publikation: Bidrag til tidsskriftKommentar/debatForskningpeer review

  1. Tumour-reactive T cell subsets in the microenvironment of ovarian cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. The real-world impact of modern treatments on the survival of patients with metastatic melanoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. High frequencies of circulating memory T cells specific for calreticulin exon 9 mutations in healthy individuals

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Immune regulation by fibroblasts in tissue injury depends on uPARAP-mediated uptake of collectins

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Principles of adoptive T cell therapy in cancer

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

Vis graf over relationer

BACKGROUND: Excessive 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).

METHODS: Type 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.

RESULTS: We 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.

CONCLUSIONS: ECM 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.

OriginalsprogEngelsk
TidsskriftJournal for ImmunoTherapy of Cancer
Vol/bind6
Udgave nummer1
Sider (fra-til)152
ISSN2051-1426
DOI
StatusUdgivet - 19 dec. 2018

ID: 56133714