Granzyme B Degraded Type IV Collagen Products in Serum Identify Melanoma Patients Responding to Immune Checkpoint Blockade
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Granzyme B Degraded Type IV Collagen Products in Serum Identify Melanoma Patients Responding to Immune Checkpoint Blockade. / Jensen, Christina; Sinkeviciute, Dovile; Madsen, Daniel Hargbol; Onnerfjord, Patrik; Hansen, Morten; Schmidt, Henrik; Karsdal, Morten Asser; Svane, Inge Marie; Willumsen, Nicholas.
I: Cancers, Bind 12, Nr. 10, 2786, 2020, s. 1-15.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Granzyme B Degraded Type IV Collagen Products in Serum Identify Melanoma Patients Responding to Immune Checkpoint Blockade
AU - Jensen, Christina
AU - Sinkeviciute, Dovile
AU - Madsen, Daniel Hargbol
AU - Onnerfjord, Patrik
AU - Hansen, Morten
AU - Schmidt, Henrik
AU - Karsdal, Morten Asser
AU - Svane, Inge Marie
AU - Willumsen, Nicholas
PY - 2020
Y1 - 2020
N2 - Simple SummaryNovel biomarkers that can identify melanoma patients responding to immune checkpoint inhibitor therapy are urgently needed. As high T-cell infiltration and low fibrotic activity are associated with response, we aimed to examine the serum biomarker potential of granzyme B degraded type IV collagen (C4G) products in combination with the fibrosis biomarker PRO-C3. We found that high C4G combined with low PRO-C3 has the potential to identify patients responding to immune checkpoint inhibitor therapy suggesting that these biomarkers may provide a non-invasive tool for patient selection and therapeutic decision-making in the future.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 (n = 54). The C4G assay was found specific for a granzyme B-generated neo-epitope on type IV collagen. The objective response rate (ORR) was 2.6-fold higher (18% vs. 7%) in patients with high C4G levels (>25th percentile) vs. low levels (
AB - Simple SummaryNovel biomarkers that can identify melanoma patients responding to immune checkpoint inhibitor therapy are urgently needed. As high T-cell infiltration and low fibrotic activity are associated with response, we aimed to examine the serum biomarker potential of granzyme B degraded type IV collagen (C4G) products in combination with the fibrosis biomarker PRO-C3. We found that high C4G combined with low PRO-C3 has the potential to identify patients responding to immune checkpoint inhibitor therapy suggesting that these biomarkers may provide a non-invasive tool for patient selection and therapeutic decision-making in the future.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 (n = 54). The C4G assay was found specific for a granzyme B-generated neo-epitope on type IV collagen. The objective response rate (ORR) was 2.6-fold higher (18% vs. 7%) in patients with high C4G levels (>25th percentile) vs. low levels (
KW - tumor microenvironment
KW - extracellular matrix
KW - collagen
KW - fibrosis
KW - T-cell infiltration
KW - biomarker
KW - immunotherapy
KW - immune checkpoint inhibitor
KW - ipilimumab
KW - melanoma
KW - CANCER PROGRESSION
KW - PREDICTIVE BIOMARKER
KW - IMMUNOTHERAPY
KW - SURVIVAL
KW - MATRIX
U2 - 10.3390/cancers12102786
DO - 10.3390/cancers12102786
M3 - Journal article
C2 - 32998446
VL - 12
SP - 1
EP - 15
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 10
M1 - 2786
ER -
ID: 251410298