Discovery of chemotherapy‐associated ovarian cancer antigens by interrogating memory T cells
According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8+ and CD4+ T‐cell responses against tumor cells. To discover chemotherapy‐associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemoth...
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Veröffentlicht in: | International Journal of Cancer. Journal International Du Cancer 2014-04, Vol.134 (8), p.1823-1834 |
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creator | Paroli, Marino Bellati, Filippo Videtta, Melissa Focaccetti, Chiara Mancone, Carmine Donato, Tiziana Antonilli, Morena Perniola, Giorgia Accapezzato, Daniele Napoletano, Chiara Nuti, Marianna Bartolazzi, Armando Panici, Pierluigi Benedetti Tripodi, Marco Palombo, Fabio Barnaba, Vincenzo |
description | According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8+ and CD4+ T‐cell responses against tumor cells. To discover chemotherapy‐associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemotherapy protocols) were interrogated with proteins isolated from primary OC cells. We screened for immunogenicity using two‐dimensional electrophoresis gel‐eluted OC proteins. Only the selected immunogenic antigens were molecularly characterized by mass‐spectrometry‐based analysis. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were correlated with prolonged survival in response to chemotherapy, supporting the model of chemotherapy‐induced apoptosis as an adjuvant of anti‐tumor immunity. The strength of both memory CD4+ and CD8+ T cells producing either IFN‐γ or IL‐17 in response to apoptotic OC antigens was also significantly greater in Responders to chemotherapy than in nonresponders. Immunogenicity of some of these antigens was confirmed using recombinant proteins in an independent set of patients. The T‐cell interrogation system represents a strategy of reverse tumor immunology that proposes to identify CAAs, which may then be validated as possible prognostic tumor biomarkers or cancer vaccines.
What's new?
According to the immunogenic cell‐death hypothesis, chemotherapy can induce CD8+ and CD4+ T‐cell responses against tumor cells. The trigger is thought to be the release of additional tumor antigens from dying tumor cells. This paper describes a “reverse immunology” technique called a T‐cell interrogation system, for identifying chemotherapy‐associated antigens (CAAs) in ovarian cancer patients. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were also correlated with prolonged survival in response to chemotherapy. This suggests that immune responses induced by immunogenic cell death may enhance current therapy. |
doi_str_mv | 10.1002/ijc.28515 |
format | Article |
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What's new?
According to the immunogenic cell‐death hypothesis, chemotherapy can induce CD8+ and CD4+ T‐cell responses against tumor cells. The trigger is thought to be the release of additional tumor antigens from dying tumor cells. This paper describes a “reverse immunology” technique called a T‐cell interrogation system, for identifying chemotherapy‐associated antigens (CAAs) in ovarian cancer patients. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were also correlated with prolonged survival in response to chemotherapy. This suggests that immune responses induced by immunogenic cell death may enhance current therapy.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.28515</identifier><identifier>PMID: 24150888</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>Hoboken, NJ: Wiley-Blackwell</publisher><subject>Adult ; Aged ; Antigens ; Antigens, Neoplasm - immunology ; Apoptosis ; Apoptosis - immunology ; Biological and medical sciences ; Cancer ; Cancer therapies ; CD8-Positive T-Lymphocytes - immunology ; Cell Survival ; Chemotherapy ; chemotherapy associated antigens ; Dendritic Cells - immunology ; Female ; Female genital diseases ; Gynecology. Andrology. Obstetrics ; Human health and pathology ; Humans ; Hypotheses ; Immunologic Memory - immunology ; Immunology ; Interferon-gamma - biosynthesis ; Interleukin-17 - biosynthesis ; Life Sciences ; Lymphocytes ; Medical research ; Medical sciences ; Middle Aged ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Ovarian cancer ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - immunology ; Proteins ; Questioning ; reverse immunology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; T cell receptors ; Th1 cells ; Th1 Cells - immunology ; Th17 cells ; tumor biomarkers ; Tumor Cells, Cultured ; Tumors</subject><ispartof>International Journal of Cancer. Journal International Du Cancer, 2014-04, Vol.134 (8), p.1823-1834</ispartof><rights>2013 UICC</rights><rights>2015 INIST-CNRS</rights><rights>2013 UICC.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4555-8f7e3a11f55a348dc5bb5468439548b1d1ca73cdd9b7cbada659cf96c0ddb0323</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.28515$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.28515$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28222481$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24150888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://riip.hal.science/pasteur-01148396$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Paroli, Marino</creatorcontrib><creatorcontrib>Bellati, Filippo</creatorcontrib><creatorcontrib>Videtta, Melissa</creatorcontrib><creatorcontrib>Focaccetti, Chiara</creatorcontrib><creatorcontrib>Mancone, Carmine</creatorcontrib><creatorcontrib>Donato, Tiziana</creatorcontrib><creatorcontrib>Antonilli, Morena</creatorcontrib><creatorcontrib>Perniola, Giorgia</creatorcontrib><creatorcontrib>Accapezzato, Daniele</creatorcontrib><creatorcontrib>Napoletano, Chiara</creatorcontrib><creatorcontrib>Nuti, Marianna</creatorcontrib><creatorcontrib>Bartolazzi, Armando</creatorcontrib><creatorcontrib>Panici, Pierluigi Benedetti</creatorcontrib><creatorcontrib>Tripodi, Marco</creatorcontrib><creatorcontrib>Palombo, Fabio</creatorcontrib><creatorcontrib>Barnaba, Vincenzo</creatorcontrib><title>Discovery of chemotherapy‐associated ovarian cancer antigens by interrogating memory T cells</title><title>International Journal of Cancer. Journal International Du Cancer</title><addtitle>Int J Cancer</addtitle><description>According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8+ and CD4+ T‐cell responses against tumor cells. To discover chemotherapy‐associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemotherapy protocols) were interrogated with proteins isolated from primary OC cells. We screened for immunogenicity using two‐dimensional electrophoresis gel‐eluted OC proteins. Only the selected immunogenic antigens were molecularly characterized by mass‐spectrometry‐based analysis. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were correlated with prolonged survival in response to chemotherapy, supporting the model of chemotherapy‐induced apoptosis as an adjuvant of anti‐tumor immunity. The strength of both memory CD4+ and CD8+ T cells producing either IFN‐γ or IL‐17 in response to apoptotic OC antigens was also significantly greater in Responders to chemotherapy than in nonresponders. Immunogenicity of some of these antigens was confirmed using recombinant proteins in an independent set of patients. The T‐cell interrogation system represents a strategy of reverse tumor immunology that proposes to identify CAAs, which may then be validated as possible prognostic tumor biomarkers or cancer vaccines.
What's new?
According to the immunogenic cell‐death hypothesis, chemotherapy can induce CD8+ and CD4+ T‐cell responses against tumor cells. The trigger is thought to be the release of additional tumor antigens from dying tumor cells. This paper describes a “reverse immunology” technique called a T‐cell interrogation system, for identifying chemotherapy‐associated antigens (CAAs) in ovarian cancer patients. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were also correlated with prolonged survival in response to chemotherapy. This suggests that immune responses induced by immunogenic cell death may enhance current therapy.</description><subject>Adult</subject><subject>Aged</subject><subject>Antigens</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Apoptosis</subject><subject>Apoptosis - immunology</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Survival</subject><subject>Chemotherapy</subject><subject>chemotherapy associated antigens</subject><subject>Dendritic Cells - immunology</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Immunologic Memory - immunology</subject><subject>Immunology</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interleukin-17 - biosynthesis</subject><subject>Life Sciences</subject><subject>Lymphocytes</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - immunology</subject><subject>Proteins</subject><subject>Questioning</subject><subject>reverse immunology</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>T cell receptors</subject><subject>Th1 cells</subject><subject>Th1 Cells - immunology</subject><subject>Th17 cells</subject><subject>tumor biomarkers</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks9u1DAQxi1ERZfCgRdAkRASl7Qe_0mcY7X8aauVuJQr1sRxdr1K4sVOFuXGI_CMPAlud1uknjjNSPPTp_lmPkLeAD0HStmF25pzpiTIZ2QBtCpzykA-J4s0o3kJvDglL2PcUgogqXhBTplIjVJqQb5_dNH4vQ1z5tvMbGzvx40NuJv__PqNMXrjcLRN5vcYHA6ZwcHYkOEwurUdYlbPmRtGG4Jf4-iGddYnhSR2mxnbdfEVOWmxi_b1sZ6Rb58_3S6v8tXXL9fLy1VuhJQyV21pOQK0UiIXqjGyrqUolOCVFKqGBgyW3DRNVZemxgYLWZm2Kgxtmppyxs9IftDdYKd3wfUYZu3R6avLld5hHO0UdLIvFK-KPST-w4HfBf9jsnHUfbpD2hgH66eoQQLjDDiI_0CpELLktEjouyfo1k9hSMY1iEoUJRRUJertkZrq3jaP6z48JQHvjwBGg10b0s1d_McpxphQdyYuDtxP19n5cQ5U36VCp1To-1To65vlfcP_AkHgqUk</recordid><startdate>20140415</startdate><enddate>20140415</enddate><creator>Paroli, Marino</creator><creator>Bellati, Filippo</creator><creator>Videtta, Melissa</creator><creator>Focaccetti, Chiara</creator><creator>Mancone, Carmine</creator><creator>Donato, Tiziana</creator><creator>Antonilli, Morena</creator><creator>Perniola, Giorgia</creator><creator>Accapezzato, Daniele</creator><creator>Napoletano, Chiara</creator><creator>Nuti, Marianna</creator><creator>Bartolazzi, Armando</creator><creator>Panici, Pierluigi Benedetti</creator><creator>Tripodi, Marco</creator><creator>Palombo, Fabio</creator><creator>Barnaba, Vincenzo</creator><general>Wiley-Blackwell</general><general>Wiley Subscription Services, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope></search><sort><creationdate>20140415</creationdate><title>Discovery of chemotherapy‐associated ovarian cancer antigens by interrogating memory T cells</title><author>Paroli, Marino ; Bellati, Filippo ; Videtta, Melissa ; Focaccetti, Chiara ; Mancone, Carmine ; Donato, Tiziana ; Antonilli, Morena ; Perniola, Giorgia ; Accapezzato, Daniele ; Napoletano, Chiara ; Nuti, Marianna ; Bartolazzi, Armando ; Panici, Pierluigi Benedetti ; Tripodi, Marco ; Palombo, Fabio ; Barnaba, Vincenzo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4555-8f7e3a11f55a348dc5bb5468439548b1d1ca73cdd9b7cbada659cf96c0ddb0323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antigens</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Apoptosis</topic><topic>Apoptosis - immunology</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell Survival</topic><topic>Chemotherapy</topic><topic>chemotherapy associated antigens</topic><topic>Dendritic Cells - immunology</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Immunologic Memory - immunology</topic><topic>Immunology</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Interleukin-17 - biosynthesis</topic><topic>Life Sciences</topic><topic>Lymphocytes</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - immunology</topic><topic>Proteins</topic><topic>Questioning</topic><topic>reverse immunology</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>T cell receptors</topic><topic>Th1 cells</topic><topic>Th1 Cells - immunology</topic><topic>Th17 cells</topic><topic>tumor biomarkers</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paroli, Marino</creatorcontrib><creatorcontrib>Bellati, Filippo</creatorcontrib><creatorcontrib>Videtta, Melissa</creatorcontrib><creatorcontrib>Focaccetti, Chiara</creatorcontrib><creatorcontrib>Mancone, Carmine</creatorcontrib><creatorcontrib>Donato, Tiziana</creatorcontrib><creatorcontrib>Antonilli, Morena</creatorcontrib><creatorcontrib>Perniola, Giorgia</creatorcontrib><creatorcontrib>Accapezzato, Daniele</creatorcontrib><creatorcontrib>Napoletano, Chiara</creatorcontrib><creatorcontrib>Nuti, Marianna</creatorcontrib><creatorcontrib>Bartolazzi, Armando</creatorcontrib><creatorcontrib>Panici, Pierluigi Benedetti</creatorcontrib><creatorcontrib>Tripodi, Marco</creatorcontrib><creatorcontrib>Palombo, Fabio</creatorcontrib><creatorcontrib>Barnaba, Vincenzo</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>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>International Journal of Cancer. Journal International Du Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paroli, Marino</au><au>Bellati, Filippo</au><au>Videtta, Melissa</au><au>Focaccetti, Chiara</au><au>Mancone, Carmine</au><au>Donato, Tiziana</au><au>Antonilli, Morena</au><au>Perniola, Giorgia</au><au>Accapezzato, Daniele</au><au>Napoletano, Chiara</au><au>Nuti, Marianna</au><au>Bartolazzi, Armando</au><au>Panici, Pierluigi Benedetti</au><au>Tripodi, Marco</au><au>Palombo, Fabio</au><au>Barnaba, Vincenzo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of chemotherapy‐associated ovarian cancer antigens by interrogating memory T cells</atitle><jtitle>International Journal of Cancer. Journal International Du Cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2014-04-15</date><risdate>2014</risdate><volume>134</volume><issue>8</issue><spage>1823</spage><epage>1834</epage><pages>1823-1834</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8+ and CD4+ T‐cell responses against tumor cells. To discover chemotherapy‐associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemotherapy protocols) were interrogated with proteins isolated from primary OC cells. We screened for immunogenicity using two‐dimensional electrophoresis gel‐eluted OC proteins. Only the selected immunogenic antigens were molecularly characterized by mass‐spectrometry‐based analysis. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were correlated with prolonged survival in response to chemotherapy, supporting the model of chemotherapy‐induced apoptosis as an adjuvant of anti‐tumor immunity. The strength of both memory CD4+ and CD8+ T cells producing either IFN‐γ or IL‐17 in response to apoptotic OC antigens was also significantly greater in Responders to chemotherapy than in nonresponders. Immunogenicity of some of these antigens was confirmed using recombinant proteins in an independent set of patients. The T‐cell interrogation system represents a strategy of reverse tumor immunology that proposes to identify CAAs, which may then be validated as possible prognostic tumor biomarkers or cancer vaccines.
What's new?
According to the immunogenic cell‐death hypothesis, chemotherapy can induce CD8+ and CD4+ T‐cell responses against tumor cells. The trigger is thought to be the release of additional tumor antigens from dying tumor cells. This paper describes a “reverse immunology” technique called a T‐cell interrogation system, for identifying chemotherapy‐associated antigens (CAAs) in ovarian cancer patients. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were also correlated with prolonged survival in response to chemotherapy. This suggests that immune responses induced by immunogenic cell death may enhance current therapy.</abstract><cop>Hoboken, NJ</cop><pub>Wiley-Blackwell</pub><pmid>24150888</pmid><doi>10.1002/ijc.28515</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Antigens Antigens, Neoplasm - immunology Apoptosis Apoptosis - immunology Biological and medical sciences Cancer Cancer therapies CD8-Positive T-Lymphocytes - immunology Cell Survival Chemotherapy chemotherapy associated antigens Dendritic Cells - immunology Female Female genital diseases Gynecology. Andrology. Obstetrics Human health and pathology Humans Hypotheses Immunologic Memory - immunology Immunology Interferon-gamma - biosynthesis Interleukin-17 - biosynthesis Life Sciences Lymphocytes Medical research Medical sciences Middle Aged Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Ovarian cancer Ovarian Neoplasms - drug therapy Ovarian Neoplasms - immunology Proteins Questioning reverse immunology Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization T cell receptors Th1 cells Th1 Cells - immunology Th17 cells tumor biomarkers Tumor Cells, Cultured Tumors |
title | Discovery of chemotherapy‐associated ovarian cancer antigens by interrogating memory T cells |
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