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Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy

To identify potential early biomarkers of treatment response and immune-related adverse events (irAE), a pilot immune monitoring study was performed in stage IV melanoma patients by flow cytometric analysis of peripheral blood mononuclear cells (PBMC). Overall, 17 patients were treated with either n...

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Autores principales: Reschke, Robin, Gussek, Philipp, Boldt, Andreas, Sack, Ulrich, Köhl, Ulrike, Lordick, Florian, Gora, Thomas, Kreuz, Markus, Reiche, Kristin, Simon, Jan-Christoph, Ziemer, Mirjana, Kunz, Manfred
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348898/
https://www.ncbi.nlm.nih.gov/pubmed/34360781
http://dx.doi.org/10.3390/ijms22158017
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author Reschke, Robin
Gussek, Philipp
Boldt, Andreas
Sack, Ulrich
Köhl, Ulrike
Lordick, Florian
Gora, Thomas
Kreuz, Markus
Reiche, Kristin
Simon, Jan-Christoph
Ziemer, Mirjana
Kunz, Manfred
author_facet Reschke, Robin
Gussek, Philipp
Boldt, Andreas
Sack, Ulrich
Köhl, Ulrike
Lordick, Florian
Gora, Thomas
Kreuz, Markus
Reiche, Kristin
Simon, Jan-Christoph
Ziemer, Mirjana
Kunz, Manfred
author_sort Reschke, Robin
collection PubMed
description To identify potential early biomarkers of treatment response and immune-related adverse events (irAE), a pilot immune monitoring study was performed in stage IV melanoma patients by flow cytometric analysis of peripheral blood mononuclear cells (PBMC). Overall, 17 patients were treated with either nivolumab or pembrolizumab alone, or with a combination of nivolumab and ipilimumab every three weeks. Of 15 patients for which complete response assessment was available, treatment responders (n = 10) as compared to non-responders (n = 5) were characterized by enhanced PD-1 expression on CD8(+) T cells immediately before treatment (median ± median absolute deviation/MAD 26.7 ± 10.4% vs. 17.2 ± 5.3%). Responders showed a higher T cell responsiveness after T cell receptor ex vivo stimulation as determined by measurement of programmed cell death 1 (PD-1) expression on CD3(+) T cells before the second cycle of treatment. The percentage of CD8(+) effector memory (CD8(+)CD45RA(−)CD45RO(+)CCR7(−)) T cells was higher in responders compared to non-responders before and immediately after the first cycle of treatment (median ± MAD 39.2 ± 7.3% vs. 30.5 ± 4.1% and 37.7 ± 4.6 vs. 24.0 ± 6.4). Immune-related adverse events (irAE) were accompanied by a higher percentage of activated CD4(+) (CD4(+)CD38(+)HLADR(+)) T cells before the second treatment cycle (median ± MAD 14.9 ± 3.9% vs. 5.3 ± 0.4%). In summary, PBMC immune monitoring of immune-checkpoint inhibition (ICI) treatment in melanoma appears to be a promising approach to identify early markers of treatment response and irAEs.
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spelling pubmed-83488982021-08-08 Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy Reschke, Robin Gussek, Philipp Boldt, Andreas Sack, Ulrich Köhl, Ulrike Lordick, Florian Gora, Thomas Kreuz, Markus Reiche, Kristin Simon, Jan-Christoph Ziemer, Mirjana Kunz, Manfred Int J Mol Sci Article To identify potential early biomarkers of treatment response and immune-related adverse events (irAE), a pilot immune monitoring study was performed in stage IV melanoma patients by flow cytometric analysis of peripheral blood mononuclear cells (PBMC). Overall, 17 patients were treated with either nivolumab or pembrolizumab alone, or with a combination of nivolumab and ipilimumab every three weeks. Of 15 patients for which complete response assessment was available, treatment responders (n = 10) as compared to non-responders (n = 5) were characterized by enhanced PD-1 expression on CD8(+) T cells immediately before treatment (median ± median absolute deviation/MAD 26.7 ± 10.4% vs. 17.2 ± 5.3%). Responders showed a higher T cell responsiveness after T cell receptor ex vivo stimulation as determined by measurement of programmed cell death 1 (PD-1) expression on CD3(+) T cells before the second cycle of treatment. The percentage of CD8(+) effector memory (CD8(+)CD45RA(−)CD45RO(+)CCR7(−)) T cells was higher in responders compared to non-responders before and immediately after the first cycle of treatment (median ± MAD 39.2 ± 7.3% vs. 30.5 ± 4.1% and 37.7 ± 4.6 vs. 24.0 ± 6.4). Immune-related adverse events (irAE) were accompanied by a higher percentage of activated CD4(+) (CD4(+)CD38(+)HLADR(+)) T cells before the second treatment cycle (median ± MAD 14.9 ± 3.9% vs. 5.3 ± 0.4%). In summary, PBMC immune monitoring of immune-checkpoint inhibition (ICI) treatment in melanoma appears to be a promising approach to identify early markers of treatment response and irAEs. MDPI 2021-07-27 /pmc/articles/PMC8348898/ /pubmed/34360781 http://dx.doi.org/10.3390/ijms22158017 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Reschke, Robin
Gussek, Philipp
Boldt, Andreas
Sack, Ulrich
Köhl, Ulrike
Lordick, Florian
Gora, Thomas
Kreuz, Markus
Reiche, Kristin
Simon, Jan-Christoph
Ziemer, Mirjana
Kunz, Manfred
Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy
title Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy
title_full Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy
title_fullStr Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy
title_full_unstemmed Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy
title_short Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy
title_sort distinct immune signatures indicative of treatment response and immune-related adverse events in melanoma patients under immune checkpoint inhibitor therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348898/
https://www.ncbi.nlm.nih.gov/pubmed/34360781
http://dx.doi.org/10.3390/ijms22158017
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