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Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma

BACKGROUND: The need for reliable clinical biomarkers to predict which patients with melanoma will benefit from immune checkpoint blockade (ICB) remains unmet. Several different parameters have been considered in the past, including routine differential blood counts, T cell subset distribution patte...

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Autores principales: Gaißler, Andrea, Bochem, Jonas, Spreuer, Janine, Ottmann, Shannon, Martens, Alexander, Amaral, Teresa, Wagner, Nikolaus Benjamin, Claassen, Manfred, Meier, Friedegund, Terheyden, Patrick, Garbe, Claus, Eigentler, Thomas, Weide, Benjamin, Pawelec, Graham, Wistuba-Hamprecht, Kilian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254874/
https://www.ncbi.nlm.nih.gov/pubmed/37286306
http://dx.doi.org/10.1136/jitc-2023-006802
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author Gaißler, Andrea
Bochem, Jonas
Spreuer, Janine
Ottmann, Shannon
Martens, Alexander
Amaral, Teresa
Wagner, Nikolaus Benjamin
Claassen, Manfred
Meier, Friedegund
Terheyden, Patrick
Garbe, Claus
Eigentler, Thomas
Weide, Benjamin
Pawelec, Graham
Wistuba-Hamprecht, Kilian
author_facet Gaißler, Andrea
Bochem, Jonas
Spreuer, Janine
Ottmann, Shannon
Martens, Alexander
Amaral, Teresa
Wagner, Nikolaus Benjamin
Claassen, Manfred
Meier, Friedegund
Terheyden, Patrick
Garbe, Claus
Eigentler, Thomas
Weide, Benjamin
Pawelec, Graham
Wistuba-Hamprecht, Kilian
author_sort Gaißler, Andrea
collection PubMed
description BACKGROUND: The need for reliable clinical biomarkers to predict which patients with melanoma will benefit from immune checkpoint blockade (ICB) remains unmet. Several different parameters have been considered in the past, including routine differential blood counts, T cell subset distribution patterns and quantification of peripheral myeloid-derived suppressor cells (MDSC), but none has yet achieved sufficient accuracy for clinical utility. METHODS: Here, we investigated potential cellular biomarkers from clinical routine blood counts as well as several myeloid and T cell subsets, using flow cytometry, in two independent cohorts of a total of 141 patients with stage IV M1c melanoma before and during ICB. RESULTS: Elevated baseline frequencies of monocytic MDSCs (M-MDSC) in the blood were confirmed to predict shorter overall survival (OS) (HR 2.086, p=0.030) and progression-free survival (HR 2.425, p=0.001) in the whole patient cohort. However, we identified a subgroup of patients with highly elevated baseline M-MDSC frequencies that fell below a defined cut-off during therapy and found that these patients had a longer OS that was similar to that of patients with low baseline M-MDSC frequencies. Importantly, patients with high M-MDSC frequencies exhibited a skewed baseline distribution of certain other immune cells but these did not influence patient survival, illustrating the paramount utility of MDSC assessment. CONCLUSION: We confirmed that in general, highly elevated frequencies of peripheral M-MDSC are associated with poorer outcomes of ICB in metastatic melanoma. However, one reason for an imperfect correlation between high baseline MDSCs and outcome for individual patients may be the subgroup of patients identified here, with rapidly decreasing M-MDSCs on therapy, in whom the negative effect of high M-MDSC frequencies was lost. These findings might contribute to developing more reliable predictors of late-stage melanoma response to ICB at the individual patient level. A multifactorial model seeking such markers yielded only MDSC behavior and serum lactate dehydrogenase as predictors of treatment outcome.
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spelling pubmed-102548742023-06-10 Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma Gaißler, Andrea Bochem, Jonas Spreuer, Janine Ottmann, Shannon Martens, Alexander Amaral, Teresa Wagner, Nikolaus Benjamin Claassen, Manfred Meier, Friedegund Terheyden, Patrick Garbe, Claus Eigentler, Thomas Weide, Benjamin Pawelec, Graham Wistuba-Hamprecht, Kilian J Immunother Cancer Immunotherapy Biomarkers BACKGROUND: The need for reliable clinical biomarkers to predict which patients with melanoma will benefit from immune checkpoint blockade (ICB) remains unmet. Several different parameters have been considered in the past, including routine differential blood counts, T cell subset distribution patterns and quantification of peripheral myeloid-derived suppressor cells (MDSC), but none has yet achieved sufficient accuracy for clinical utility. METHODS: Here, we investigated potential cellular biomarkers from clinical routine blood counts as well as several myeloid and T cell subsets, using flow cytometry, in two independent cohorts of a total of 141 patients with stage IV M1c melanoma before and during ICB. RESULTS: Elevated baseline frequencies of monocytic MDSCs (M-MDSC) in the blood were confirmed to predict shorter overall survival (OS) (HR 2.086, p=0.030) and progression-free survival (HR 2.425, p=0.001) in the whole patient cohort. However, we identified a subgroup of patients with highly elevated baseline M-MDSC frequencies that fell below a defined cut-off during therapy and found that these patients had a longer OS that was similar to that of patients with low baseline M-MDSC frequencies. Importantly, patients with high M-MDSC frequencies exhibited a skewed baseline distribution of certain other immune cells but these did not influence patient survival, illustrating the paramount utility of MDSC assessment. CONCLUSION: We confirmed that in general, highly elevated frequencies of peripheral M-MDSC are associated with poorer outcomes of ICB in metastatic melanoma. However, one reason for an imperfect correlation between high baseline MDSCs and outcome for individual patients may be the subgroup of patients identified here, with rapidly decreasing M-MDSCs on therapy, in whom the negative effect of high M-MDSC frequencies was lost. These findings might contribute to developing more reliable predictors of late-stage melanoma response to ICB at the individual patient level. A multifactorial model seeking such markers yielded only MDSC behavior and serum lactate dehydrogenase as predictors of treatment outcome. BMJ Publishing Group 2023-06-07 /pmc/articles/PMC10254874/ /pubmed/37286306 http://dx.doi.org/10.1136/jitc-2023-006802 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.
spellingShingle Immunotherapy Biomarkers
Gaißler, Andrea
Bochem, Jonas
Spreuer, Janine
Ottmann, Shannon
Martens, Alexander
Amaral, Teresa
Wagner, Nikolaus Benjamin
Claassen, Manfred
Meier, Friedegund
Terheyden, Patrick
Garbe, Claus
Eigentler, Thomas
Weide, Benjamin
Pawelec, Graham
Wistuba-Hamprecht, Kilian
Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma
title Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma
title_full Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma
title_fullStr Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma
title_full_unstemmed Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma
title_short Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma
title_sort early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma
topic Immunotherapy Biomarkers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254874/
https://www.ncbi.nlm.nih.gov/pubmed/37286306
http://dx.doi.org/10.1136/jitc-2023-006802
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