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
Hauptverfasser: 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
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container_end_page 1834
container_issue 8
container_start_page 1823
container_title International Journal of Cancer. Journal International Du Cancer
container_volume 134
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
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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. 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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. 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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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