Granzyme B Degraded Type IV Collagen Products in Serum Identify Melanoma Patients Responding to Immune Checkpoint Blockade.

T-cell infiltration biomarker collagen extracellular matrix fibrosis immune checkpoint inhibitor immunotherapy ipilimumab melanoma tumor microenvironment

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
28 Sep 2020
Historique:
received: 04 08 2020
revised: 23 09 2020
accepted: 26 09 2020
entrez: 1 10 2020
pubmed: 2 10 2020
medline: 2 10 2020
Statut: epublish

Résumé

A T-cell permissive tumor microenvironment, characterized by the presence of activated T cells and low fibrotic activity is crucial for response to immune checkpoint inhibitors (ICIs). Granzyme B has been shown to promote T-cell migration through the basement membrane by the degradation of type IV collagen. In this study, we evaluated the biomarker potential of measuring granzyme B-mediated degradation of type IV collagen (C4G) in combination with a fibroblast activation biomarker (PRO-C3) non-invasively for identifying metastatic melanoma patients responding to the ICI ipilimumab. A monoclonal antibody was generated against C4G and used to develop a competitive electro-chemiluminescence immunoassay. C4G and PRO-C3 were measured in pretreatment serum from metastatic melanoma patients (

Identifiants

pubmed: 32998446
pii: cancers12102786
doi: 10.3390/cancers12102786
pmc: PMC7601429
pii:
doi:

Types de publication

Journal Article

Langues

eng

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Auteurs

Christina Jensen (C)

Biomarkers & Research, Nordic Bioscience, 2730 Herlev, Denmark.
Biotech Research & Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.

Dovile Sinkeviciute (D)

Biomarkers & Research, Nordic Bioscience, 2730 Herlev, Denmark.
Department of Clinical Sciences Lund, Lund University, 221 84 Lund, Sweden.

Daniel Hargbøl Madsen (DH)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, 2730 Herlev, Denmark.

Patrik Önnerfjord (P)

Department of Clinical Sciences Lund, Lund University, 221 84 Lund, Sweden.

Morten Hansen (M)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, 2730 Herlev, Denmark.

Henrik Schmidt (H)

Department of Oncology, Aarhus University Hospital, 8200 Aarhus, Denmark.

Morten Asser Karsdal (MA)

Biomarkers & Research, Nordic Bioscience, 2730 Herlev, Denmark.

Inge Marie Svane (IM)

National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, 2730 Herlev, Denmark.

Nicholas Willumsen (N)

Biomarkers & Research, Nordic Bioscience, 2730 Herlev, Denmark.

Classifications MeSH