Serum CD163 and TARC as Disease Response Biomarkers in Classical Hodgkin Lymphoma
Candidate circulating disease response biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin-Reed-Sternberg (HRS) cells or nonmalignant tumor-infiltrating cells. HRS cells are sparse within the diseased node, whereas benign CD163(+) M2 tissue-associated macrophages (TAM) are promi...
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| Veröffentlicht in: | Clinical cancer research 2013-02, Vol.19 (3), p.731-742 |
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| creator | JONES, Kimberley VARI, Frank KEANE, Colm CROOKS, Pauline NOURSE, Jamie P SEYMOUR, Louise A GOTTLIEB, David RITCHIE, David GILL, Devinder GANDHI, Maher K |
| description | Candidate circulating disease response biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin-Reed-Sternberg (HRS) cells or nonmalignant tumor-infiltrating cells. HRS cells are sparse within the diseased node, whereas benign CD163(+) M2 tissue-associated macrophages (TAM) are prominent. CD163(+) cells within the malignant node may be prognostic, but there is no data on serum CD163 (sCD163). The HRS-specific serum protein sTARC shows promise as a disease response biomarker. Tumor-specific and tumor-infiltrating circulating biomarkers have not been compared previously.
We prospectively measured sCD163 and sTARC in 221 samples from 47 patients with Hodgkin lymphoma and 21 healthy participants. Blood was taken at five fixed time-points prior, during, and after first-line therapy. Results were compared with radiological assessment and plasma Epstein-Barr virus DNA (EBV-DNA). Potential sources of circulating CD163 were investigated, along with immunosuppressive properties of CD163.
Pretherapy, both sCD163 and sTARC were markedly elevated compared with healthy and complete remission samples. sCD163 better reflected tumor burden during therapy, whereas sTARC had greater value upon completion of therapy. sCD163 correlated with plasma EBV-DNA, and associated with B symptoms, stage, and lymphopenia. Circulating CD163(+) monocytes were elevated in patients, indicating that sCD163 are likely derived from circulating and intratumoral cells. Depletion of cHL CD163(+) monocytes markedly enhanced T-cell proliferation, implicating monocytes and/or TAMs as potential novel targets for immunotherapeutic manipulation.
The combination of circulating tumor-infiltrate (sCD163) and tumor-specific (sTARC) proteins is more informative than either marker alone as disease response biomarkers in early and advanced disease during first-line therapy for cHL. |
| doi_str_mv | 10.1158/1078-0432.ccr-12-2693 |
| format | Article |
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We prospectively measured sCD163 and sTARC in 221 samples from 47 patients with Hodgkin lymphoma and 21 healthy participants. Blood was taken at five fixed time-points prior, during, and after first-line therapy. Results were compared with radiological assessment and plasma Epstein-Barr virus DNA (EBV-DNA). Potential sources of circulating CD163 were investigated, along with immunosuppressive properties of CD163.
Pretherapy, both sCD163 and sTARC were markedly elevated compared with healthy and complete remission samples. sCD163 better reflected tumor burden during therapy, whereas sTARC had greater value upon completion of therapy. sCD163 correlated with plasma EBV-DNA, and associated with B symptoms, stage, and lymphopenia. Circulating CD163(+) monocytes were elevated in patients, indicating that sCD163 are likely derived from circulating and intratumoral cells. Depletion of cHL CD163(+) monocytes markedly enhanced T-cell proliferation, implicating monocytes and/or TAMs as potential novel targets for immunotherapeutic manipulation.
The combination of circulating tumor-infiltrate (sCD163) and tumor-specific (sTARC) proteins is more informative than either marker alone as disease response biomarkers in early and advanced disease during first-line therapy for cHL.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.ccr-12-2693</identifier><identifier>PMID: 23224400</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adolescent ; Adult ; Aged ; Antigens, CD - blood ; Antigens, CD - metabolism ; Antigens, Differentiation, Myelomonocytic - blood ; Antigens, Differentiation, Myelomonocytic - metabolism ; Antineoplastic agents ; Biological and medical sciences ; Biomarkers - blood ; Chemokine CCL17 - blood ; Female ; Hematologic and hematopoietic diseases ; Hodgkin Disease - blood ; Hodgkin Disease - immunology ; Hodgkin Disease - pathology ; Humans ; Hypersensitivity - blood ; Hypersensitivity - immunology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lipopolysaccharide Receptors - metabolism ; Lymphocyte Count ; Male ; Medical sciences ; Middle Aged ; Monocytes - metabolism ; Neoplasm Staging ; Pharmacology. Drug treatments ; Prognosis ; Receptors, Cell Surface - blood ; Receptors, Cell Surface - metabolism ; Sensitivity and Specificity ; T-Lymphocytes - immunology ; Treatment Outcome ; Young Adult</subject><ispartof>Clinical cancer research, 2013-02, Vol.19 (3), p.731-742</ispartof><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-8d2e1a074771741f7498c7c1ccc2dd7a45124b3496280e44ca9e4bcab7ea1a003</citedby><cites>FETCH-LOGICAL-c452t-8d2e1a074771741f7498c7c1ccc2dd7a45124b3496280e44ca9e4bcab7ea1a003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,3360,27933,27934</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27061928$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23224400$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JONES, Kimberley</creatorcontrib><creatorcontrib>VARI, Frank</creatorcontrib><creatorcontrib>KEANE, Colm</creatorcontrib><creatorcontrib>CROOKS, Pauline</creatorcontrib><creatorcontrib>NOURSE, Jamie P</creatorcontrib><creatorcontrib>SEYMOUR, Louise A</creatorcontrib><creatorcontrib>GOTTLIEB, David</creatorcontrib><creatorcontrib>RITCHIE, David</creatorcontrib><creatorcontrib>GILL, Devinder</creatorcontrib><creatorcontrib>GANDHI, Maher K</creatorcontrib><title>Serum CD163 and TARC as Disease Response Biomarkers in Classical Hodgkin Lymphoma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Candidate circulating disease response biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin-Reed-Sternberg (HRS) cells or nonmalignant tumor-infiltrating cells. HRS cells are sparse within the diseased node, whereas benign CD163(+) M2 tissue-associated macrophages (TAM) are prominent. CD163(+) cells within the malignant node may be prognostic, but there is no data on serum CD163 (sCD163). The HRS-specific serum protein sTARC shows promise as a disease response biomarker. Tumor-specific and tumor-infiltrating circulating biomarkers have not been compared previously.
We prospectively measured sCD163 and sTARC in 221 samples from 47 patients with Hodgkin lymphoma and 21 healthy participants. Blood was taken at five fixed time-points prior, during, and after first-line therapy. Results were compared with radiological assessment and plasma Epstein-Barr virus DNA (EBV-DNA). Potential sources of circulating CD163 were investigated, along with immunosuppressive properties of CD163.
Pretherapy, both sCD163 and sTARC were markedly elevated compared with healthy and complete remission samples. sCD163 better reflected tumor burden during therapy, whereas sTARC had greater value upon completion of therapy. sCD163 correlated with plasma EBV-DNA, and associated with B symptoms, stage, and lymphopenia. Circulating CD163(+) monocytes were elevated in patients, indicating that sCD163 are likely derived from circulating and intratumoral cells. Depletion of cHL CD163(+) monocytes markedly enhanced T-cell proliferation, implicating monocytes and/or TAMs as potential novel targets for immunotherapeutic manipulation.
The combination of circulating tumor-infiltrate (sCD163) and tumor-specific (sTARC) proteins is more informative than either marker alone as disease response biomarkers in early and advanced disease during first-line therapy for cHL.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antigens, CD - blood</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, Differentiation, Myelomonocytic - blood</subject><subject>Antigens, Differentiation, Myelomonocytic - metabolism</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Chemokine CCL17 - blood</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hodgkin Disease - blood</subject><subject>Hodgkin Disease - immunology</subject><subject>Hodgkin Disease - pathology</subject><subject>Humans</subject><subject>Hypersensitivity - blood</subject><subject>Hypersensitivity - immunology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lipopolysaccharide Receptors - metabolism</subject><subject>Lymphocyte Count</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Monocytes - metabolism</subject><subject>Neoplasm Staging</subject><subject>Pharmacology. Drug treatments</subject><subject>Prognosis</subject><subject>Receptors, Cell Surface - blood</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Sensitivity and Specificity</subject><subject>T-Lymphocytes - immunology</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1PwzAMhiME4vsngHJB4lKIU7dpj9DxJU1CjHGO0jSDsn6MeD3w70nFBidb1vPa8sPYGYgrgCS7BqGySGAsr6z1EchIpnm8ww4hSVQUyzTZDf2WOWBHRJ9CAILAfXYgYykRhThkL6_ODy0vJpDG3HQVn9_MCm6IT2pyhhyfOVr1XWhu6741fuk88brjRWOIamsa_thX78swmX63q4-AnLC9hWnInW7qMXu7v5sXj9H0-eGpuJlGFhO5jrJKOjBCoVKgEBYK88wqC9ZaWVXKYAISyxjzVGbCIVqTOyytKZUzISfiY3b5u3fl-6_B0Vq3NVnXNKZz_UAaZIYyS1KEgCa_qPU9kXcLvfJ1eOZbg9CjTT2a0qMpXRSzENWjzZA735wYytZVf6mtvgBcbABDwcXCm87W9M8pkUIus_gHzu97Lg</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>JONES, Kimberley</creator><creator>VARI, Frank</creator><creator>KEANE, Colm</creator><creator>CROOKS, Pauline</creator><creator>NOURSE, Jamie P</creator><creator>SEYMOUR, Louise A</creator><creator>GOTTLIEB, David</creator><creator>RITCHIE, David</creator><creator>GILL, Devinder</creator><creator>GANDHI, Maher K</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130201</creationdate><title>Serum CD163 and TARC as Disease Response Biomarkers in Classical Hodgkin Lymphoma</title><author>JONES, Kimberley ; VARI, Frank ; KEANE, Colm ; CROOKS, Pauline ; NOURSE, Jamie P ; SEYMOUR, Louise A ; GOTTLIEB, David ; RITCHIE, David ; GILL, Devinder ; GANDHI, Maher K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-8d2e1a074771741f7498c7c1ccc2dd7a45124b3496280e44ca9e4bcab7ea1a003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antigens, CD - blood</topic><topic>Antigens, CD - metabolism</topic><topic>Antigens, Differentiation, Myelomonocytic - blood</topic><topic>Antigens, Differentiation, Myelomonocytic - metabolism</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Chemokine CCL17 - blood</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hodgkin Disease - blood</topic><topic>Hodgkin Disease - immunology</topic><topic>Hodgkin Disease - pathology</topic><topic>Humans</topic><topic>Hypersensitivity - blood</topic><topic>Hypersensitivity - immunology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lipopolysaccharide Receptors - metabolism</topic><topic>Lymphocyte Count</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Monocytes - metabolism</topic><topic>Neoplasm Staging</topic><topic>Pharmacology. Drug treatments</topic><topic>Prognosis</topic><topic>Receptors, Cell Surface - blood</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Sensitivity and Specificity</topic><topic>T-Lymphocytes - immunology</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JONES, Kimberley</creatorcontrib><creatorcontrib>VARI, Frank</creatorcontrib><creatorcontrib>KEANE, Colm</creatorcontrib><creatorcontrib>CROOKS, Pauline</creatorcontrib><creatorcontrib>NOURSE, Jamie P</creatorcontrib><creatorcontrib>SEYMOUR, Louise A</creatorcontrib><creatorcontrib>GOTTLIEB, David</creatorcontrib><creatorcontrib>RITCHIE, David</creatorcontrib><creatorcontrib>GILL, Devinder</creatorcontrib><creatorcontrib>GANDHI, Maher K</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JONES, Kimberley</au><au>VARI, Frank</au><au>KEANE, Colm</au><au>CROOKS, Pauline</au><au>NOURSE, Jamie P</au><au>SEYMOUR, Louise A</au><au>GOTTLIEB, David</au><au>RITCHIE, David</au><au>GILL, Devinder</au><au>GANDHI, Maher K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum CD163 and TARC as Disease Response Biomarkers in Classical Hodgkin Lymphoma</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>19</volume><issue>3</issue><spage>731</spage><epage>742</epage><pages>731-742</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract>Candidate circulating disease response biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin-Reed-Sternberg (HRS) cells or nonmalignant tumor-infiltrating cells. HRS cells are sparse within the diseased node, whereas benign CD163(+) M2 tissue-associated macrophages (TAM) are prominent. CD163(+) cells within the malignant node may be prognostic, but there is no data on serum CD163 (sCD163). The HRS-specific serum protein sTARC shows promise as a disease response biomarker. Tumor-specific and tumor-infiltrating circulating biomarkers have not been compared previously.
We prospectively measured sCD163 and sTARC in 221 samples from 47 patients with Hodgkin lymphoma and 21 healthy participants. Blood was taken at five fixed time-points prior, during, and after first-line therapy. Results were compared with radiological assessment and plasma Epstein-Barr virus DNA (EBV-DNA). Potential sources of circulating CD163 were investigated, along with immunosuppressive properties of CD163.
Pretherapy, both sCD163 and sTARC were markedly elevated compared with healthy and complete remission samples. sCD163 better reflected tumor burden during therapy, whereas sTARC had greater value upon completion of therapy. sCD163 correlated with plasma EBV-DNA, and associated with B symptoms, stage, and lymphopenia. Circulating CD163(+) monocytes were elevated in patients, indicating that sCD163 are likely derived from circulating and intratumoral cells. Depletion of cHL CD163(+) monocytes markedly enhanced T-cell proliferation, implicating monocytes and/or TAMs as potential novel targets for immunotherapeutic manipulation.
The combination of circulating tumor-infiltrate (sCD163) and tumor-specific (sTARC) proteins is more informative than either marker alone as disease response biomarkers in early and advanced disease during first-line therapy for cHL.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>23224400</pmid><doi>10.1158/1078-0432.ccr-12-2693</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Antigens, CD - blood Antigens, CD - metabolism Antigens, Differentiation, Myelomonocytic - blood Antigens, Differentiation, Myelomonocytic - metabolism Antineoplastic agents Biological and medical sciences Biomarkers - blood Chemokine CCL17 - blood Female Hematologic and hematopoietic diseases Hodgkin Disease - blood Hodgkin Disease - immunology Hodgkin Disease - pathology Humans Hypersensitivity - blood Hypersensitivity - immunology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lipopolysaccharide Receptors - metabolism Lymphocyte Count Male Medical sciences Middle Aged Monocytes - metabolism Neoplasm Staging Pharmacology. Drug treatments Prognosis Receptors, Cell Surface - blood Receptors, Cell Surface - metabolism Sensitivity and Specificity T-Lymphocytes - immunology Treatment Outcome Young Adult |
| title | Serum CD163 and TARC as Disease Response Biomarkers in Classical Hodgkin Lymphoma |
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