Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein

Sonja I Buschow; Matteo Ramazzotti; Inge M J Reinieren-Beeren; Lucie M Heinzerling; Harm Westdorp; Irene Stefanini; Luca Beltrame; Stanleyson V Hato; Eva Ellebaek; Stefanie Gross; Van Anh Nguyen; Georg Weinlich; Jiannis Ragoussis; Dilair Baban; Beatrice Schuler-Thurner; Inge M Svane; Nikolaus Romani; Jonathan M Austyn; I Jolanda M De Vries; Gerold Schuler; Duccio Cavalieri; Carl G Figdor

doi:10.18632/oncotarget.18698

Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein

Sonja I Buschow, Matteo Ramazzotti, Inge M J Reinieren-Beeren, Lucie M Heinzerling, Harm Westdorp, Irene Stefanini, Luca Beltrame, Stanleyson V Hato, Eva Ellebaek, Stefanie Gross, Van Anh Nguyen, Georg Weinlich, Jiannis Ragoussis, Dilair Baban, Beatrice Schuler-Thurner, Inge M Svane, Nikolaus Romani, Jonathan M Austyn, I Jolanda M De Vries, Gerold SchulerDuccio Cavalieri, Carl G Figdor

Institut for Klinisk Medicin

12 Citationer (Scopus)

96 Downloads (Pure)

Abstract

Immunotherapy for metastatic melanoma offers great promise but, to date, only a subset of patients have responded. There is an urgent need to identify ways of allocating patients to the most beneficial therapy, to increase survival and decrease therapy-associated morbidity and costs. Blood-based biomarkers are of particular interest because of their straightforward implementation in routine clinical care. We sought to identify markers for dendritic cell (DC) vaccine-based immunotherapy against metastatic melanoma through gene expression analysis of peripheral blood mononuclear cells. A large-scale microarray analysis of 74 samples from two treatment centers, taken directly after the first round of DC vaccination, was performed. We found that phosphatidylethanolamine binding protein 1 (PEBP1)/Raf Kinase inhibitory protein (RKIP) expression can be used to identify a significant proportion of patients who performed poorly after DC vaccination. This result was validated by q-PCR analysis on blood samples from a second cohort of 95 patients treated with DC vaccination in four different centers. We conclude that low PEBP1 expression correlates with poor overall survival after DC vaccination. Intriguingly, this was only the case for expression of PEBP1 after, but not prior to, DC vaccination. Moreover, the change in PEBP1 expression upon vaccination correlated well with survival. Further analyses revealed that PEBP1 expression positively correlated with genes involved in T cell responses but inversely correlated with genes associated with myeloid cells and aberrant inflammation including STAT3, NOTCH1, and MAPK1. Concordantly, PEBP1 inversely correlated with the myeloid/lymphoid-ratio and was suppressed in patients suffering from chronic inflammatory disease.

Originalsprog	Engelsk
Tidsskrift	OncoTarget
Vol/bind	8
Udgave nummer	40
Sider (fra-til)	67439-67456
Antal sider	18
ISSN	1949-2553
DOI	https://doi.org/10.18632/oncotarget.18698
Status	Udgivet - 2017

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10.18632/oncotarget.18698Licens: CC BY

Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory proteinForlagets udgivne version, 3,77 MBLicens: CC BY

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Buschow, S. I., Ramazzotti, M., Reinieren-Beeren, I. M. J., Heinzerling, L. M., Westdorp, H., Stefanini, I., Beltrame, L., Hato, S. V., Ellebaek, E., Gross, S., Nguyen, V. A., Weinlich, G., Ragoussis, J., Baban, D., Schuler-Thurner, B., Svane, I. M., Romani, N., Austyn, J. M., De Vries, I. J. M., ... Figdor, C. G. (2017). Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein. OncoTarget, 8(40), 67439-67456. https://doi.org/10.18632/oncotarget.18698

Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein. / Buschow, Sonja I; Ramazzotti, Matteo; Reinieren-Beeren, Inge M J et al.
I: OncoTarget, Bind 8, Nr. 40, 2017, s. 67439-67456.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Buschow, SI, Ramazzotti, M, Reinieren-Beeren, IMJ, Heinzerling, LM, Westdorp, H, Stefanini, I, Beltrame, L, Hato, SV, Ellebaek, E, Gross, S, Nguyen, VA, Weinlich, G, Ragoussis, J, Baban, D, Schuler-Thurner, B, Svane, IM, Romani, N, Austyn, JM, De Vries, IJM, Schuler, G, Cavalieri, D & Figdor, CG 2017, 'Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein', OncoTarget, bind 8, nr. 40, s. 67439-67456. https://doi.org/10.18632/oncotarget.18698

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title = "Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein",

abstract = "Immunotherapy for metastatic melanoma offers great promise but, to date, only a subset of patients have responded. There is an urgent need to identify ways of allocating patients to the most beneficial therapy, to increase survival and decrease therapy-associated morbidity and costs. Blood-based biomarkers are of particular interest because of their straightforward implementation in routine clinical care. We sought to identify markers for dendritic cell (DC) vaccine-based immunotherapy against metastatic melanoma through gene expression analysis of peripheral blood mononuclear cells. A large-scale microarray analysis of 74 samples from two treatment centers, taken directly after the first round of DC vaccination, was performed. We found that phosphatidylethanolamine binding protein 1 (PEBP1)/Raf Kinase inhibitory protein (RKIP) expression can be used to identify a significant proportion of patients who performed poorly after DC vaccination. This result was validated by q-PCR analysis on blood samples from a second cohort of 95 patients treated with DC vaccination in four different centers. We conclude that low PEBP1 expression correlates with poor overall survival after DC vaccination. Intriguingly, this was only the case for expression of PEBP1 after, but not prior to, DC vaccination. Moreover, the change in PEBP1 expression upon vaccination correlated well with survival. Further analyses revealed that PEBP1 expression positively correlated with genes involved in T cell responses but inversely correlated with genes associated with myeloid cells and aberrant inflammation including STAT3, NOTCH1, and MAPK1. Concordantly, PEBP1 inversely correlated with the myeloid/lymphoid-ratio and was suppressed in patients suffering from chronic inflammatory disease.",

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T1 - Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein

AU - Buschow, Sonja I

AU - Ramazzotti, Matteo

AU - Reinieren-Beeren, Inge M J

AU - Heinzerling, Lucie M

AU - Westdorp, Harm

AU - Stefanini, Irene

AU - Beltrame, Luca

AU - Hato, Stanleyson V

AU - Ellebaek, Eva

AU - Gross, Stefanie

AU - Nguyen, Van Anh

AU - Weinlich, Georg

AU - Ragoussis, Jiannis

AU - Baban, Dilair

AU - Schuler-Thurner, Beatrice

AU - Svane, Inge M

AU - Romani, Nikolaus

AU - Austyn, Jonathan M

AU - De Vries, I Jolanda M

AU - Schuler, Gerold

AU - Cavalieri, Duccio

AU - Figdor, Carl G

PY - 2017

Y1 - 2017

N2 - Immunotherapy for metastatic melanoma offers great promise but, to date, only a subset of patients have responded. There is an urgent need to identify ways of allocating patients to the most beneficial therapy, to increase survival and decrease therapy-associated morbidity and costs. Blood-based biomarkers are of particular interest because of their straightforward implementation in routine clinical care. We sought to identify markers for dendritic cell (DC) vaccine-based immunotherapy against metastatic melanoma through gene expression analysis of peripheral blood mononuclear cells. A large-scale microarray analysis of 74 samples from two treatment centers, taken directly after the first round of DC vaccination, was performed. We found that phosphatidylethanolamine binding protein 1 (PEBP1)/Raf Kinase inhibitory protein (RKIP) expression can be used to identify a significant proportion of patients who performed poorly after DC vaccination. This result was validated by q-PCR analysis on blood samples from a second cohort of 95 patients treated with DC vaccination in four different centers. We conclude that low PEBP1 expression correlates with poor overall survival after DC vaccination. Intriguingly, this was only the case for expression of PEBP1 after, but not prior to, DC vaccination. Moreover, the change in PEBP1 expression upon vaccination correlated well with survival. Further analyses revealed that PEBP1 expression positively correlated with genes involved in T cell responses but inversely correlated with genes associated with myeloid cells and aberrant inflammation including STAT3, NOTCH1, and MAPK1. Concordantly, PEBP1 inversely correlated with the myeloid/lymphoid-ratio and was suppressed in patients suffering from chronic inflammatory disease.

AB - Immunotherapy for metastatic melanoma offers great promise but, to date, only a subset of patients have responded. There is an urgent need to identify ways of allocating patients to the most beneficial therapy, to increase survival and decrease therapy-associated morbidity and costs. Blood-based biomarkers are of particular interest because of their straightforward implementation in routine clinical care. We sought to identify markers for dendritic cell (DC) vaccine-based immunotherapy against metastatic melanoma through gene expression analysis of peripheral blood mononuclear cells. A large-scale microarray analysis of 74 samples from two treatment centers, taken directly after the first round of DC vaccination, was performed. We found that phosphatidylethanolamine binding protein 1 (PEBP1)/Raf Kinase inhibitory protein (RKIP) expression can be used to identify a significant proportion of patients who performed poorly after DC vaccination. This result was validated by q-PCR analysis on blood samples from a second cohort of 95 patients treated with DC vaccination in four different centers. We conclude that low PEBP1 expression correlates with poor overall survival after DC vaccination. Intriguingly, this was only the case for expression of PEBP1 after, but not prior to, DC vaccination. Moreover, the change in PEBP1 expression upon vaccination correlated well with survival. Further analyses revealed that PEBP1 expression positively correlated with genes involved in T cell responses but inversely correlated with genes associated with myeloid cells and aberrant inflammation including STAT3, NOTCH1, and MAPK1. Concordantly, PEBP1 inversely correlated with the myeloid/lymphoid-ratio and was suppressed in patients suffering from chronic inflammatory disease.

KW - Journal Article

U2 - 10.18632/oncotarget.18698

DO - 10.18632/oncotarget.18698

M3 - Journal article

C2 - 28978044

SN - 1949-2553

VL - 8

SP - 67439

EP - 67456

JO - OncoTarget

JF - OncoTarget

IS - 40

ER -

Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein

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