Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies
Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibo...
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| Veröffentlicht in: | PloS one 2011-04, Vol.6 (4), p.e19330-e19330 |
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| creator | Gilbert, Amy E Karagiannis, Panagiotis Dodev, Tihomir Koers, Alexander Lacy, Katie Josephs, Debra H Takhar, Pooja Geh, Jenny L C Healy, Ciaran Harries, Mark Acland, Katharine M Rudman, Sarah M Beavil, Rebecca L Blower, Philip J Beavil, Andrew J Gould, Hannah J Spicer, James Nestle, Frank O Karagiannis, Sophia N |
| description | Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P |
| doi_str_mv | 10.1371/journal.pone.0019330 |
| format | Article |
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While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0019330</identifier><identifier>PMID: 21559411</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antibodies, Monoclonal - chemistry ; Antibodies, Neoplasm - chemistry ; B cells ; B-Lymphocytes - immunology ; Biology ; Cancer ; Cancer metastasis ; Case-Control Studies ; Cell Line ; Cell Line, Tumor ; Cohort Studies ; Comparative analysis ; Cytotoxicity ; Development and progression ; Disease Progression ; Enzyme-linked immunosorbent assay ; Enzyme-Linked Immunosorbent Assay - methods ; Fibroblasts - metabolism ; Humans ; IgG antibody ; Immune response (cell-mediated) ; Immune response (humoral) ; Immune System ; Immunogenicity ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunoglobulin G - chemistry ; Immunohistochemistry - methods ; Immunological memory ; Immunotherapy ; Lymphocytes B ; Lymphocytes T ; Medicine ; Melanoma ; Melanoma - blood ; Melanoma - immunology ; Melanoma - therapy ; Metastases ; Monoclonal antibodies ; Ovarian cancer ; Patients ; Peripheral blood ; Skin ; Skin cancer ; Skin diseases ; T cell receptors ; T cells ; Time Factors ; Toxicity</subject><ispartof>PloS one, 2011-04, Vol.6 (4), p.e19330-e19330</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>Copyright Public Library of Science Apr 2011</rights><rights>Gilbert et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-2011489c5d4f9a09e7dc0890ccf7ca4fffe6d729dcc71ac071b4dc8db14c158f3</citedby><cites>FETCH-LOGICAL-c757t-2011489c5d4f9a09e7dc0890ccf7ca4fffe6d729dcc71ac071b4dc8db14c158f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084832/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084832/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21559411$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gilbert, Amy E</creatorcontrib><creatorcontrib>Karagiannis, Panagiotis</creatorcontrib><creatorcontrib>Dodev, Tihomir</creatorcontrib><creatorcontrib>Koers, Alexander</creatorcontrib><creatorcontrib>Lacy, Katie</creatorcontrib><creatorcontrib>Josephs, Debra H</creatorcontrib><creatorcontrib>Takhar, Pooja</creatorcontrib><creatorcontrib>Geh, Jenny L C</creatorcontrib><creatorcontrib>Healy, Ciaran</creatorcontrib><creatorcontrib>Harries, Mark</creatorcontrib><creatorcontrib>Acland, Katharine M</creatorcontrib><creatorcontrib>Rudman, Sarah M</creatorcontrib><creatorcontrib>Beavil, Rebecca L</creatorcontrib><creatorcontrib>Blower, Philip J</creatorcontrib><creatorcontrib>Beavil, Andrew J</creatorcontrib><creatorcontrib>Gould, Hannah J</creatorcontrib><creatorcontrib>Spicer, James</creatorcontrib><creatorcontrib>Nestle, Frank O</creatorcontrib><creatorcontrib>Karagiannis, Sophia N</creatorcontrib><title>Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.</description><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibodies, Neoplasm - chemistry</subject><subject>B cells</subject><subject>B-Lymphocytes - immunology</subject><subject>Biology</subject><subject>Cancer</subject><subject>Cancer metastasis</subject><subject>Case-Control Studies</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cohort Studies</subject><subject>Comparative analysis</subject><subject>Cytotoxicity</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Enzyme-Linked Immunosorbent Assay - methods</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>IgG antibody</subject><subject>Immune response (cell-mediated)</subject><subject>Immune response (humoral)</subject><subject>Immune System</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin G - chemistry</subject><subject>Immunohistochemistry - methods</subject><subject>Immunological memory</subject><subject>Immunotherapy</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Medicine</subject><subject>Melanoma</subject><subject>Melanoma - blood</subject><subject>Melanoma - immunology</subject><subject>Melanoma - therapy</subject><subject>Metastases</subject><subject>Monoclonal antibodies</subject><subject>Ovarian cancer</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Skin</subject><subject>Skin cancer</subject><subject>Skin diseases</subject><subject>T cell receptors</subject><subject>T cells</subject><subject>Time 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the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies</title><author>Gilbert, Amy E ; Karagiannis, Panagiotis ; Dodev, Tihomir ; Koers, Alexander ; Lacy, Katie ; Josephs, Debra H ; Takhar, Pooja ; Geh, Jenny L C ; Healy, Ciaran ; Harries, Mark ; Acland, Katharine M ; Rudman, Sarah M ; Beavil, Rebecca L ; Blower, Philip J ; Beavil, Andrew J ; Gould, Hannah J ; Spicer, James ; Nestle, Frank O ; Karagiannis, Sophia N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-2011489c5d4f9a09e7dc0890ccf7ca4fffe6d729dcc71ac071b4dc8db14c158f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antibodies, Neoplasm - chemistry</topic><topic>B cells</topic><topic>B-Lymphocytes - immunology</topic><topic>Biology</topic><topic>Cancer</topic><topic>Cancer metastasis</topic><topic>Case-Control 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therapy</topic><topic>Metastases</topic><topic>Monoclonal antibodies</topic><topic>Ovarian cancer</topic><topic>Patients</topic><topic>Peripheral blood</topic><topic>Skin</topic><topic>Skin cancer</topic><topic>Skin diseases</topic><topic>T cell receptors</topic><topic>T cells</topic><topic>Time Factors</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gilbert, Amy E</creatorcontrib><creatorcontrib>Karagiannis, Panagiotis</creatorcontrib><creatorcontrib>Dodev, Tihomir</creatorcontrib><creatorcontrib>Koers, Alexander</creatorcontrib><creatorcontrib>Lacy, Katie</creatorcontrib><creatorcontrib>Josephs, Debra H</creatorcontrib><creatorcontrib>Takhar, Pooja</creatorcontrib><creatorcontrib>Geh, Jenny L C</creatorcontrib><creatorcontrib>Healy, Ciaran</creatorcontrib><creatorcontrib>Harries, Mark</creatorcontrib><creatorcontrib>Acland, Katharine M</creatorcontrib><creatorcontrib>Rudman, Sarah 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One</addtitle><date>2011-04-29</date><risdate>2011</risdate><volume>6</volume><issue>4</issue><spage>e19330</spage><epage>e19330</epage><pages>e19330-e19330</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21559411</pmid><doi>10.1371/journal.pone.0019330</doi><tpages>e19330</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| recordid | cdi_plos_journals_1296534943 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Antibodies, Monoclonal - chemistry Antibodies, Neoplasm - chemistry B cells B-Lymphocytes - immunology Biology Cancer Cancer metastasis Case-Control Studies Cell Line Cell Line, Tumor Cohort Studies Comparative analysis Cytotoxicity Development and progression Disease Progression Enzyme-linked immunosorbent assay Enzyme-Linked Immunosorbent Assay - methods Fibroblasts - metabolism Humans IgG antibody Immune response (cell-mediated) Immune response (humoral) Immune System Immunogenicity Immunoglobulin G Immunoglobulin G - blood Immunoglobulin G - chemistry Immunohistochemistry - methods Immunological memory Immunotherapy Lymphocytes B Lymphocytes T Medicine Melanoma Melanoma - blood Melanoma - immunology Melanoma - therapy Metastases Monoclonal antibodies Ovarian cancer Patients Peripheral blood Skin Skin cancer Skin diseases T cell receptors T cells Time Factors Toxicity |
| title | Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T12%3A31%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Monitoring%20the%20systemic%20human%20memory%20B%20cell%20compartment%20of%20melanoma%20patients%20for%20anti-tumor%20IgG%20antibodies&rft.jtitle=PloS%20one&rft.au=Gilbert,%20Amy%20E&rft.date=2011-04-29&rft.volume=6&rft.issue=4&rft.spage=e19330&rft.epage=e19330&rft.pages=e19330-e19330&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0019330&rft_dat=%3Cgale_plos_%3EA476892501%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1296534943&rft_id=info:pmid/21559411&rft_galeid=A476892501&rft_doaj_id=oai_doaj_org_article_78cd2d0c45b44313a534ee2dfce6fb91&rfr_iscdi=true |