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Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors

Purpose: Checkpoint inhibitors have significantly improved treatment of metastatic melanoma. However, 40–60% of patients do not respond to therapy, emphasizing the need for better predictive biomarkers for treatment response to immune checkpoint inhibitors. Prorammed death-ligand 1(PD-L1) expression...

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Autores principales: Pedersen, Jesper Geert, Madsen, Anne Tranberg, Gammelgaard, Kristine Raaby, Aggerholm-Pedersen, Ninna, Sørensen, Boe Sandahl, Øllegaard, Trine Heide, Jakobsen, Martin Roelsgaard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353055/
https://www.ncbi.nlm.nih.gov/pubmed/32486146
http://dx.doi.org/10.3390/cancers12061414
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author Pedersen, Jesper Geert
Madsen, Anne Tranberg
Gammelgaard, Kristine Raaby
Aggerholm-Pedersen, Ninna
Sørensen, Boe Sandahl
Øllegaard, Trine Heide
Jakobsen, Martin Roelsgaard
author_facet Pedersen, Jesper Geert
Madsen, Anne Tranberg
Gammelgaard, Kristine Raaby
Aggerholm-Pedersen, Ninna
Sørensen, Boe Sandahl
Øllegaard, Trine Heide
Jakobsen, Martin Roelsgaard
author_sort Pedersen, Jesper Geert
collection PubMed
description Purpose: Checkpoint inhibitors have significantly improved treatment of metastatic melanoma. However, 40–60% of patients do not respond to therapy, emphasizing the need for better predictive biomarkers for treatment response to immune checkpoint inhibitors. Prorammed death-ligand 1(PD-L1) expression in tumor cells is currently used as a predictive biomarker; however, it lacks specificity. Therefore, it is of utmost importance to identify other novel biomarkers that can predict treatment outcome. Experimental design: We studied a small cohort of 16 patients with advanced-stage melanoma treated with first-line checkpoint inhibitors. Plasma samples were collected prior to treatment initiation and continuously during the first year of treatment. Circulating tumor DNA (ctDNA) level and the expression of ten inflammatory cytokines were analyzed. Results: We found that the ctDNA-level in a blood sample collected after 6–8 weeks of therapy is predictive for response to checkpoint inhibitors. Patients with undetectable ctDNA had significantly longer progression-free survival (PFS) compared with patients with detectable ctDNA (median 26.3 vs. 2.1 months, p = 0.006). In parallel, we identified that high levels of the cytokines monocyte chemoattractant protein 1 (MCP1) and tumor necrosis factor α(TNFα) in baseline blood samples were significantly associated with longer PFS compared to low level of these cytokines (median not reached vs. 8.2 months p = 0.0008). Conclusions: These findings suggest that the levels of ctDNA, MCP1, and TNFα in baseline and early follow-up samples can predict disease progression in metastatic melanoma patients treated with checkpoint inhibitors. Potentially, these minimally invasive biomarkers may identify responders from non-responders.
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spelling pubmed-73530552020-07-15 Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors Pedersen, Jesper Geert Madsen, Anne Tranberg Gammelgaard, Kristine Raaby Aggerholm-Pedersen, Ninna Sørensen, Boe Sandahl Øllegaard, Trine Heide Jakobsen, Martin Roelsgaard Cancers (Basel) Article Purpose: Checkpoint inhibitors have significantly improved treatment of metastatic melanoma. However, 40–60% of patients do not respond to therapy, emphasizing the need for better predictive biomarkers for treatment response to immune checkpoint inhibitors. Prorammed death-ligand 1(PD-L1) expression in tumor cells is currently used as a predictive biomarker; however, it lacks specificity. Therefore, it is of utmost importance to identify other novel biomarkers that can predict treatment outcome. Experimental design: We studied a small cohort of 16 patients with advanced-stage melanoma treated with first-line checkpoint inhibitors. Plasma samples were collected prior to treatment initiation and continuously during the first year of treatment. Circulating tumor DNA (ctDNA) level and the expression of ten inflammatory cytokines were analyzed. Results: We found that the ctDNA-level in a blood sample collected after 6–8 weeks of therapy is predictive for response to checkpoint inhibitors. Patients with undetectable ctDNA had significantly longer progression-free survival (PFS) compared with patients with detectable ctDNA (median 26.3 vs. 2.1 months, p = 0.006). In parallel, we identified that high levels of the cytokines monocyte chemoattractant protein 1 (MCP1) and tumor necrosis factor α(TNFα) in baseline blood samples were significantly associated with longer PFS compared to low level of these cytokines (median not reached vs. 8.2 months p = 0.0008). Conclusions: These findings suggest that the levels of ctDNA, MCP1, and TNFα in baseline and early follow-up samples can predict disease progression in metastatic melanoma patients treated with checkpoint inhibitors. Potentially, these minimally invasive biomarkers may identify responders from non-responders. MDPI 2020-05-30 /pmc/articles/PMC7353055/ /pubmed/32486146 http://dx.doi.org/10.3390/cancers12061414 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pedersen, Jesper Geert
Madsen, Anne Tranberg
Gammelgaard, Kristine Raaby
Aggerholm-Pedersen, Ninna
Sørensen, Boe Sandahl
Øllegaard, Trine Heide
Jakobsen, Martin Roelsgaard
Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors
title Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors
title_full Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors
title_fullStr Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors
title_full_unstemmed Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors
title_short Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors
title_sort inflammatory cytokines and ctdna are biomarkers for progression in advanced-stage melanoma patients receiving checkpoint inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353055/
https://www.ncbi.nlm.nih.gov/pubmed/32486146
http://dx.doi.org/10.3390/cancers12061414
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