Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma
Identifieur interne : 007A01 ( Ncbi/Merge ); précédent : 007A00; suivant : 007A02Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma
Auteurs : Panagiotis Karagiannis [Royaume-Uni, Allemagne] ; Federica Villanova [Royaume-Uni] ; Debra H. Josephs [Royaume-Uni] ; Isabel Correa [Royaume-Uni] ; Mieke Van Hemelrijck ; Carl Hobbs [Royaume-Uni] ; Louise Saul [Royaume-Uni] ; Isioma U. Egbuniwe [Royaume-Uni] ; Isabella Tosi [Royaume-Uni] ; Kristina M. Ilieva [Royaume-Uni] ; Emma Kent [Royaume-Uni] ; Eduardo Calonje [Royaume-Uni] ; Mark Harries [Royaume-Uni] ; Ian Fentiman [Royaume-Uni] ; Joyce Taylor-Papadimitriou [Royaume-Uni] ; Joy Burchell [Royaume-Uni] ; James F. Spicer [Royaume-Uni] ; Katie E. Lacy [Royaume-Uni] ; Frank O. Nestle [Royaume-Uni] ; Sophia N. Karagiannis [Royaume-Uni]Source :
- Oncoimmunology [ 2162-4011 ] ; 2015.
Abstract
Emerging evidence suggests pathological and immunoregulatory functions for IgG4 antibodies and IgG4+ B cells in inflammatory diseases and malignancies. We previously reported that IgG4 antibodies restrict activation of immune effector cell functions and impair humoral responses in melanoma. Here, we investigate IgG4 as a predictor of risk for disease progression in a study of human sera (n = 271: 167 melanoma patients; 104 healthy volunteers) and peripheral blood B cells (n = 71: 47 melanoma patients; 24 healthy volunteers). IgG4 (IgG4/IgGtotal) serum levels were elevated in melanoma. High relative IgG4 levels negatively correlated with progression-free survival (PFS) and overall survival. In early stage (I–II) disease, serum IgG4 was independently negatively prognostic for progression-free survival, as was elevation of IgG4+ circulating B cells (CD45+CD22+CD19+CD3−CD14−). In human tissues (n = 256; 108 cutaneous melanomas; 56 involved lymph nodes; 60 distant metastases; 32 normal skin samples) IgG4+ cell infiltrates were found in 42.6% of melanomas, 21.4% of involved lymph nodes and 30% of metastases, suggesting inflammatory conditions that favor IgG4 at the peripheral and local levels. Consistent with emerging evidence for an immunosuppressive role for IgG4, these findings indicate association of elevated IgG4 with disease progression and less favorable clinical outcomes. Characterizing immunoglobulin and other humoral immune profiles in melanoma might identify valuable prognostic tools for patient stratification and in the future lead to more effective treatments less prone to tumor-induced blockade mechanisms.
Url:
DOI: 10.1080/2162402X.2015.1032492
PubMed: 26451312
PubMed Central: 4590000
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<author><name sortKey="Van Hemelrijck, Mieke" sort="Van Hemelrijck, Mieke" uniqKey="Van Hemelrijck M" first="Mieke" last="Van Hemelrijck">Mieke Van Hemelrijck</name>
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</nlm:aff>
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</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Nestle, Frank O" sort="Nestle, Frank O" uniqKey="Nestle F" first="Frank O" last="Nestle">Frank O. Nestle</name>
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</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Karagiannis, Sophia N" sort="Karagiannis, Sophia N" uniqKey="Karagiannis S" first="Sophia N" last="Karagiannis">Sophia N. Karagiannis</name>
<affiliation wicri:level="1"><nlm:aff id="af0001"><institution>St. John's Institute of Dermatology; Division of Genetics and Molecular Medicine; Faculty of Life Sciences and Medicine; King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas' Hospitals and King's College London; Guy's Hospital; King's College London</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma</title>
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<affiliation wicri:level="1"><nlm:aff id="af0002"><institution>University Hospital of Hamburg Eppendorf; Department of Oncology; Hematology and Stem Cell Transplantation</institution>
; Hamburg,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Villanova, Federica" sort="Villanova, Federica" uniqKey="Villanova F" first="Federica" last="Villanova">Federica Villanova</name>
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<author><name sortKey="Josephs, Debra H" sort="Josephs, Debra H" uniqKey="Josephs D" first="Debra H" last="Josephs">Debra H. Josephs</name>
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Department of Research Oncology; Division of Cancer Studies; Faculty of Life Sciences and Medicine; King's College London; Guy's Hospital</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Correa, Isabel" sort="Correa, Isabel" uniqKey="Correa I" first="Isabel" last="Correa">Isabel Correa</name>
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<author><name sortKey="Van Hemelrijck, Mieke" sort="Van Hemelrijck, Mieke" uniqKey="Van Hemelrijck M" first="Mieke" last="Van Hemelrijck">Mieke Van Hemelrijck</name>
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; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Saul, Louise" sort="Saul, Louise" uniqKey="Saul L" first="Louise" last="Saul">Louise Saul</name>
<affiliation wicri:level="1"><nlm:aff id="af0001"><institution>St. John's Institute of Dermatology; Division of Genetics and Molecular Medicine; Faculty of Life Sciences and Medicine; King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas' Hospitals and King's College London; Guy's Hospital; King's College London</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Department of Research Oncology; Division of Cancer Studies; Faculty of Life Sciences and Medicine; King's College London; Guy's Hospital</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Egbuniwe, Isioma U" sort="Egbuniwe, Isioma U" uniqKey="Egbuniwe I" first="Isioma U" last="Egbuniwe">Isioma U. Egbuniwe</name>
<affiliation wicri:level="1"><nlm:aff id="af0001"><institution>St. John's Institute of Dermatology; Division of Genetics and Molecular Medicine; Faculty of Life Sciences and Medicine; King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas' Hospitals and King's College London; Guy's Hospital; King's College London</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Tosi, Isabella" sort="Tosi, Isabella" uniqKey="Tosi I" first="Isabella" last="Tosi">Isabella Tosi</name>
<affiliation wicri:level="1"><nlm:aff id="af0001"><institution>St. John's Institute of Dermatology; Division of Genetics and Molecular Medicine; Faculty of Life Sciences and Medicine; King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas' Hospitals and King's College London; Guy's Hospital; King's College London</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ilieva, Kristina M" sort="Ilieva, Kristina M" uniqKey="Ilieva K" first="Kristina M" last="Ilieva">Kristina M. Ilieva</name>
<affiliation wicri:level="1"><nlm:aff id="af0001"><institution>St. John's Institute of Dermatology; Division of Genetics and Molecular Medicine; Faculty of Life Sciences and Medicine; King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas' Hospitals and King's College London; Guy's Hospital; King's College London</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af0006"><institution>Breakthrough Breast Cancer Research Unit; Department of Research Oncology; Guy's Hospital; King's College London School of Medicine</institution>
; London,<country>United Kingdom</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kent, Emma" sort="Kent, Emma" uniqKey="Kent E" first="Emma" last="Kent">Emma Kent</name>
<affiliation wicri:level="1"><nlm:aff id="af0001"><institution>St. John's Institute of Dermatology; Division of Genetics and Molecular Medicine; Faculty of Life Sciences and Medicine; King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas' Hospitals and King's College London; Guy's Hospital; King's College London</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Calonje, Eduardo" sort="Calonje, Eduardo" uniqKey="Calonje E" first="Eduardo" last="Calonje">Eduardo Calonje</name>
<affiliation wicri:level="1"><nlm:aff id="af0007"><institution>Skin Tumor Unit; St. John's Institute of Dermatology; Guy's Hospital, King's College London and Guy's and St Thomas' NHS Trust</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Harries, Mark" sort="Harries, Mark" uniqKey="Harries M" first="Mark" last="Harries">Mark Harries</name>
<affiliation wicri:level="1"><nlm:aff id="af0008"><institution>Clinical Oncology; Guy's and St. Thomas's NHS Foundation Trust</institution>
, London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fentiman, Ian" sort="Fentiman, Ian" uniqKey="Fentiman I" first="Ian" last="Fentiman">Ian Fentiman</name>
<affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Department of Research Oncology; Division of Cancer Studies; Faculty of Life Sciences and Medicine; King's College London; Guy's Hospital</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Taylor Papadimitriou, Joyce" sort="Taylor Papadimitriou, Joyce" uniqKey="Taylor Papadimitriou J" first="Joyce" last="Taylor-Papadimitriou">Joyce Taylor-Papadimitriou</name>
<affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Department of Research Oncology; Division of Cancer Studies; Faculty of Life Sciences and Medicine; King's College London; Guy's Hospital</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Burchell, Joy" sort="Burchell, Joy" uniqKey="Burchell J" first="Joy" last="Burchell">Joy Burchell</name>
<affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Department of Research Oncology; Division of Cancer Studies; Faculty of Life Sciences and Medicine; King's College London; Guy's Hospital</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Spicer, James F" sort="Spicer, James F" uniqKey="Spicer J" first="James F" last="Spicer">James F. Spicer</name>
<affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Department of Research Oncology; Division of Cancer Studies; Faculty of Life Sciences and Medicine; King's College London; Guy's Hospital</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lacy, Katie E" sort="Lacy, Katie E" uniqKey="Lacy K" first="Katie E" last="Lacy">Katie E. Lacy</name>
<affiliation wicri:level="1"><nlm:aff id="af0001"><institution>St. John's Institute of Dermatology; Division of Genetics and Molecular Medicine; Faculty of Life Sciences and Medicine; King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas' Hospitals and King's College London; Guy's Hospital; King's College London</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af0007"><institution>Skin Tumor Unit; St. John's Institute of Dermatology; Guy's Hospital, King's College London and Guy's and St Thomas' NHS Trust</institution>
; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Nestle, Frank O" sort="Nestle, Frank O" uniqKey="Nestle F" first="Frank O" last="Nestle">Frank O. Nestle</name>
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; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Karagiannis, Sophia N" sort="Karagiannis, Sophia N" uniqKey="Karagiannis S" first="Sophia N" last="Karagiannis">Sophia N. Karagiannis</name>
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; London,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Oncoimmunology</title>
<idno type="ISSN">2162-4011</idno>
<idno type="eISSN">2162-402X</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Emerging evidence suggests pathological and immunoregulatory functions for IgG4 antibodies and IgG4<sup>+</sup>
B cells in inflammatory diseases and malignancies. We previously reported that IgG4 antibodies restrict activation of immune effector cell functions and impair humoral responses in melanoma. Here, we investigate IgG4 as a predictor of risk for disease progression in a study of human sera (n = 271: 167 melanoma patients; 104 healthy volunteers) and peripheral blood B cells (n = 71: 47 melanoma patients; 24 healthy volunteers). IgG4 (IgG4/IgG<sub>total</sub>
) serum levels were elevated in melanoma. High relative IgG4 levels negatively correlated with progression-free survival (PFS) and overall survival. In early stage (I–II) disease, serum IgG4 was independently negatively prognostic for progression-free survival, as was elevation of IgG4<sup>+</sup>
circulating B cells (CD45<sup>+</sup>
CD22<sup>+</sup>
CD19<sup>+</sup>
CD3<sup>−</sup>
CD14<sup>−</sup>
). In human tissues (n = 256; 108 cutaneous melanomas; 56 involved lymph nodes; 60 distant metastases; 32 normal skin samples) IgG4<sup>+</sup>
cell infiltrates were found in 42.6% of melanomas, 21.4% of involved lymph nodes and 30% of metastases, suggesting inflammatory conditions that favor IgG4 at the peripheral and local levels. Consistent with emerging evidence for an immunosuppressive role for IgG4, these findings indicate association of elevated IgG4 with disease progression and less favorable clinical outcomes. Characterizing immunoglobulin and other humoral immune profiles in melanoma might identify valuable prognostic tools for patient stratification and in the future lead to more effective treatments less prone to tumor-induced blockade mechanisms.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Oncoimmunology</journal-id>
<journal-id journal-id-type="iso-abbrev">Oncoimmunology</journal-id>
<journal-id journal-id-type="pmc">KONI</journal-id>
<journal-title-group><journal-title>Oncoimmunology</journal-title>
</journal-title-group>
<issn pub-type="ppub">2162-4011</issn>
<issn pub-type="epub">2162-402X</issn>
<publisher><publisher-name>Taylor & Francis</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26451312</article-id>
<article-id pub-id-type="pmc">4590000</article-id>
<article-id pub-id-type="publisher-id">1032492</article-id>
<article-id pub-id-type="doi">10.1080/2162402X.2015.1032492</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Original Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Karagiannis</surname>
<given-names>Panagiotis</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="af0002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Villanova</surname>
<given-names>Federica</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Josephs</surname>
<given-names>Debra H</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="af0003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Correa</surname>
<given-names>Isabel</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Van Hemelrijck</surname>
<given-names>Mieke</given-names>
</name>
<xref ref-type="aff" rid="af0004"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hobbs</surname>
<given-names>Carl</given-names>
</name>
<xref ref-type="aff" rid="af0005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Saul</surname>
<given-names>Louise</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="af0003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Egbuniwe</surname>
<given-names>Isioma U</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tosi</surname>
<given-names>Isabella</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ilieva</surname>
<given-names>Kristina M</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="af0006"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kent</surname>
<given-names>Emma</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Calonje</surname>
<given-names>Eduardo</given-names>
</name>
<xref ref-type="aff" rid="af0007"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Harries</surname>
<given-names>Mark</given-names>
</name>
<xref ref-type="aff" rid="af0008"><sup>8</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fentiman</surname>
<given-names>Ian</given-names>
</name>
<xref ref-type="aff" rid="af0003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Taylor-Papadimitriou</surname>
<given-names>Joyce</given-names>
</name>
<xref ref-type="aff" rid="af0003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Burchell</surname>
<given-names>Joy</given-names>
</name>
<xref ref-type="aff" rid="af0003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Spicer</surname>
<given-names>James F</given-names>
</name>
<xref ref-type="aff" rid="af0003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lacy</surname>
<given-names>Katie E</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="af0007"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nestle</surname>
<given-names>Frank O</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Karagiannis</surname>
<given-names>Sophia N</given-names>
</name>
<xref ref-type="aff" rid="af0001"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="an0001"><sup>*</sup>
</xref>
</contrib>
<aff id="af0001"><label>1</label>
<institution>St. John's Institute of Dermatology; Division of Genetics and Molecular Medicine; Faculty of Life Sciences and Medicine; King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas' Hospitals and King's College London; Guy's Hospital; King's College London</institution>
; London,<country>UK</country>
</aff>
<aff id="af0002"><label>2</label>
<institution>University Hospital of Hamburg Eppendorf; Department of Oncology; Hematology and Stem Cell Transplantation</institution>
; Hamburg,<country>Germany</country>
</aff>
<aff id="af0003"><label>3</label>
<institution>Department of Research Oncology; Division of Cancer Studies; Faculty of Life Sciences and Medicine; King's College London; Guy's Hospital</institution>
; London,<country>UK</country>
</aff>
<aff id="af0004"><label>4</label>
<institution>King's College London; Faculty of Life Sciences and Medicine; Division of Cancer Studies; Cancer Epidemiology Group; Guy's Hospital; London, UK</institution>
</aff>
<aff id="af0005"><label>5</label>
<institution>Wolfson Center for Age-Related Diseases; King's College London</institution>
; London,<country>UK</country>
</aff>
<aff id="af0006"><label>6</label>
<institution>Breakthrough Breast Cancer Research Unit; Department of Research Oncology; Guy's Hospital; King's College London School of Medicine</institution>
; London,<country>United Kingdom</country>
</aff>
<aff id="af0007"><label>7</label>
<institution>Skin Tumor Unit; St. John's Institute of Dermatology; Guy's Hospital, King's College London and Guy's and St Thomas' NHS Trust</institution>
; London,<country>UK</country>
</aff>
<aff id="af0008"><label>8</label>
<institution>Clinical Oncology; Guy's and St. Thomas's NHS Foundation Trust</institution>
, London,<country>UK</country>
</aff>
</contrib-group>
<author-notes><corresp id="an0001"><label>*</label>
Correspondence to: Sophia N Karagiannis; Email: <email xlink:href="sophia.karagiannis@kcl.ac.uk">sophia.karagiannis@kcl.ac.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="collection"><month>11</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>3</day>
<month>6</month>
<year>2015</year>
</pub-date>
<volume>4</volume>
<issue>11</issue>
<elocation-id seq="19">e1032492</elocation-id>
<history><date date-type="received"><day>27</day>
<month>2</month>
<year>2015</year>
</date>
<date date-type="rev-recd"><day>14</day>
<month>3</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>17</day>
<month>3</month>
<year>2015</year>
</date>
</history>
<permissions><copyright-statement>© 2015 The Author(s). Published with license by Taylor & Francis</copyright-statement>
<copyright-statement content-type="description">© Panagiotis Karagiannis, Federica Villanova, Debra H Josephs, Isabel Correa, Mieke Van Hemelrijck, Carl Hobbs, Louise Saul, Isioma U Egbuniwe, Isabella Tosi, Kristina M Ilieva, Emma Kent, Eduardo Calonje, Mark Harries, Ian Fentiman, Joyce Taylor-Papadimitriou, Joy Burchell, James F Spicer, Katie E Lacy, Frank O Nestle, and Sophia N Karagiannis</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>The Author(s)</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="koni-04-11-1032492.pdf"></self-uri>
<abstract><p>Emerging evidence suggests pathological and immunoregulatory functions for IgG4 antibodies and IgG4<sup>+</sup>
B cells in inflammatory diseases and malignancies. We previously reported that IgG4 antibodies restrict activation of immune effector cell functions and impair humoral responses in melanoma. Here, we investigate IgG4 as a predictor of risk for disease progression in a study of human sera (n = 271: 167 melanoma patients; 104 healthy volunteers) and peripheral blood B cells (n = 71: 47 melanoma patients; 24 healthy volunteers). IgG4 (IgG4/IgG<sub>total</sub>
) serum levels were elevated in melanoma. High relative IgG4 levels negatively correlated with progression-free survival (PFS) and overall survival. In early stage (I–II) disease, serum IgG4 was independently negatively prognostic for progression-free survival, as was elevation of IgG4<sup>+</sup>
circulating B cells (CD45<sup>+</sup>
CD22<sup>+</sup>
CD19<sup>+</sup>
CD3<sup>−</sup>
CD14<sup>−</sup>
). In human tissues (n = 256; 108 cutaneous melanomas; 56 involved lymph nodes; 60 distant metastases; 32 normal skin samples) IgG4<sup>+</sup>
cell infiltrates were found in 42.6% of melanomas, 21.4% of involved lymph nodes and 30% of metastases, suggesting inflammatory conditions that favor IgG4 at the peripheral and local levels. Consistent with emerging evidence for an immunosuppressive role for IgG4, these findings indicate association of elevated IgG4 with disease progression and less favorable clinical outcomes. Characterizing immunoglobulin and other humoral immune profiles in melanoma might identify valuable prognostic tools for patient stratification and in the future lead to more effective treatments less prone to tumor-induced blockade mechanisms.</p>
</abstract>
<kwd-group kwd-group-type="author"><title>Keywords</title>
<kwd>B cells</kwd>
<kwd>biomarker</kwd>
<kwd>cancer inflammation</kwd>
<kwd>humoral response</kwd>
<kwd>immunomodulation</kwd>
<kwd>immunomonitoring</kwd>
<kwd>immunosuppression</kwd>
<kwd>IgG4</kwd>
<kwd>melanoma</kwd>
<kwd>prognosis</kwd>
</kwd-group>
<counts><fig-count count="5"></fig-count>
<table-count count="1"></table-count>
<ref-count count="58"></ref-count>
<page-count count="14"></page-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Allemagne</li>
<li>Royaume-Uni</li>
</country>
</list>
<tree><noCountry><name sortKey="Van Hemelrijck, Mieke" sort="Van Hemelrijck, Mieke" uniqKey="Van Hemelrijck M" first="Mieke" last="Van Hemelrijck">Mieke Van Hemelrijck</name>
</noCountry>
<country name="Royaume-Uni"><noRegion><name sortKey="Karagiannis, Panagiotis" sort="Karagiannis, Panagiotis" uniqKey="Karagiannis P" first="Panagiotis" last="Karagiannis">Panagiotis Karagiannis</name>
</noRegion>
<name sortKey="Burchell, Joy" sort="Burchell, Joy" uniqKey="Burchell J" first="Joy" last="Burchell">Joy Burchell</name>
<name sortKey="Calonje, Eduardo" sort="Calonje, Eduardo" uniqKey="Calonje E" first="Eduardo" last="Calonje">Eduardo Calonje</name>
<name sortKey="Correa, Isabel" sort="Correa, Isabel" uniqKey="Correa I" first="Isabel" last="Correa">Isabel Correa</name>
<name sortKey="Egbuniwe, Isioma U" sort="Egbuniwe, Isioma U" uniqKey="Egbuniwe I" first="Isioma U" last="Egbuniwe">Isioma U. Egbuniwe</name>
<name sortKey="Fentiman, Ian" sort="Fentiman, Ian" uniqKey="Fentiman I" first="Ian" last="Fentiman">Ian Fentiman</name>
<name sortKey="Harries, Mark" sort="Harries, Mark" uniqKey="Harries M" first="Mark" last="Harries">Mark Harries</name>
<name sortKey="Hobbs, Carl" sort="Hobbs, Carl" uniqKey="Hobbs C" first="Carl" last="Hobbs">Carl Hobbs</name>
<name sortKey="Ilieva, Kristina M" sort="Ilieva, Kristina M" uniqKey="Ilieva K" first="Kristina M" last="Ilieva">Kristina M. Ilieva</name>
<name sortKey="Ilieva, Kristina M" sort="Ilieva, Kristina M" uniqKey="Ilieva K" first="Kristina M" last="Ilieva">Kristina M. Ilieva</name>
<name sortKey="Josephs, Debra H" sort="Josephs, Debra H" uniqKey="Josephs D" first="Debra H" last="Josephs">Debra H. Josephs</name>
<name sortKey="Josephs, Debra H" sort="Josephs, Debra H" uniqKey="Josephs D" first="Debra H" last="Josephs">Debra H. Josephs</name>
<name sortKey="Karagiannis, Sophia N" sort="Karagiannis, Sophia N" uniqKey="Karagiannis S" first="Sophia N" last="Karagiannis">Sophia N. Karagiannis</name>
<name sortKey="Kent, Emma" sort="Kent, Emma" uniqKey="Kent E" first="Emma" last="Kent">Emma Kent</name>
<name sortKey="Lacy, Katie E" sort="Lacy, Katie E" uniqKey="Lacy K" first="Katie E" last="Lacy">Katie E. Lacy</name>
<name sortKey="Lacy, Katie E" sort="Lacy, Katie E" uniqKey="Lacy K" first="Katie E" last="Lacy">Katie E. Lacy</name>
<name sortKey="Nestle, Frank O" sort="Nestle, Frank O" uniqKey="Nestle F" first="Frank O" last="Nestle">Frank O. Nestle</name>
<name sortKey="Saul, Louise" sort="Saul, Louise" uniqKey="Saul L" first="Louise" last="Saul">Louise Saul</name>
<name sortKey="Saul, Louise" sort="Saul, Louise" uniqKey="Saul L" first="Louise" last="Saul">Louise Saul</name>
<name sortKey="Spicer, James F" sort="Spicer, James F" uniqKey="Spicer J" first="James F" last="Spicer">James F. Spicer</name>
<name sortKey="Taylor Papadimitriou, Joyce" sort="Taylor Papadimitriou, Joyce" uniqKey="Taylor Papadimitriou J" first="Joyce" last="Taylor-Papadimitriou">Joyce Taylor-Papadimitriou</name>
<name sortKey="Tosi, Isabella" sort="Tosi, Isabella" uniqKey="Tosi I" first="Isabella" last="Tosi">Isabella Tosi</name>
<name sortKey="Villanova, Federica" sort="Villanova, Federica" uniqKey="Villanova F" first="Federica" last="Villanova">Federica Villanova</name>
</country>
<country name="Allemagne"><noRegion><name sortKey="Karagiannis, Panagiotis" sort="Karagiannis, Panagiotis" uniqKey="Karagiannis P" first="Panagiotis" last="Karagiannis">Panagiotis Karagiannis</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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