Eintrag weiter verarbeiten
Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide
Gespeichert in:
| Zeitschriftentitel: | International Journal of Cancer |
|---|---|
| Personen und Körperschaften: | , , , , , , , , |
| In: | International Journal of Cancer, 142, 2018, 5, S. 976-987 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Buccione, Carla Fragale, Alessandra Polverino, Federica Ziccheddu, Giovanna Aricò, Eleonora Belardelli, Filippo Proietti, Enrico Battistini, Angela Moschella, Federica Buccione, Carla Fragale, Alessandra Polverino, Federica Ziccheddu, Giovanna Aricò, Eleonora Belardelli, Filippo Proietti, Enrico Battistini, Angela Moschella, Federica |
|---|---|
| author |
Buccione, Carla Fragale, Alessandra Polverino, Federica Ziccheddu, Giovanna Aricò, Eleonora Belardelli, Filippo Proietti, Enrico Battistini, Angela Moschella, Federica |
| spellingShingle |
Buccione, Carla Fragale, Alessandra Polverino, Federica Ziccheddu, Giovanna Aricò, Eleonora Belardelli, Filippo Proietti, Enrico Battistini, Angela Moschella, Federica International Journal of Cancer Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide Cancer Research Oncology |
| author_sort |
buccione, carla |
| spelling |
Buccione, Carla Fragale, Alessandra Polverino, Federica Ziccheddu, Giovanna Aricò, Eleonora Belardelli, Filippo Proietti, Enrico Battistini, Angela Moschella, Federica 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.31083 <jats:p>The antitumor effectiveness of cyclophosphamide (CTX) and other chemotherapeutics was shown to rely not only on direct cytotoxicity but also on immunogenic tumor cell death and systemic immunomodulatory mechanisms, including regulatory T cell (Treg) depletion, Th1 cell polarization, type I interferon (IFN) and proinflammatory cytokine production. IFN regulatory factor (IRF)‐1 is a transcriptional regulator of IFNs and IFN‐inducible genes, involved in the control of Th1 and Treg differentiation and in sterile inflammation. Aim of this study was to explore the role of IRF‐1 in CTX‐induced antitumor effects and related immune activities. This study shows for the first time that IRF‐1 is important for the antitumor efficacy of CTX in mice. Moreover, experiments in tumor‐bearing C57BL/6 mice showed that <jats:italic>Irf1</jats:italic> gene expression in the spleen was transiently increased following CTX administration and correlated with the induction of Th1 cell expansion and of <jats:italic>Il12p40</jats:italic> gene expression, which is the main Th1‐driving cytokine. At the same time, CTX administration reduced both <jats:italic>Foxp3</jats:italic> expression and Treg cell percentages. These effects were abrogated in <jats:italic>Irf1<jats:sup>−/−</jats:sup></jats:italic> mice. Further experiments showed that the gene and/or protein expression of caspase‐1, iNOS, IL‐1β, IL‐6 and CXCL10 and the levels of nitric oxide were modulated following CTX in an IRF‐1‐direct‐ or ‐indirect‐dependent manner, and highlighted the importance of caspase‐1 in driving the sterile inflammatory response to CTX. Our data identify IRF‐1 as important for the antitumor efficacy of CTX and for the regulation of many immunomodulatory activities of CTX, such as Th1 polarization, Treg depletion and inflammation.</jats:p> Role of interferon regulatory factor 1 in governing <scp>T</scp>reg depletion, <scp>T</scp>h1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide International Journal of Cancer |
| doi_str_mv |
10.1002/ijc.31083 |
| facet_avail |
Online Free |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAwMi9pamMuMzEwODM |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAwMi9pamMuMzEwODM |
| institution |
DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 |
| imprint |
Wiley, 2018 |
| imprint_str_mv |
Wiley, 2018 |
| issn |
0020-7136 1097-0215 |
| issn_str_mv |
0020-7136 1097-0215 |
| language |
English |
| mega_collection |
Wiley (CrossRef) |
| match_str |
buccione2018roleofinterferonregulatoryfactor1ingoverningtregdepletionth1polarizationinflammasomeactivationandantitumorefficacyofcyclophosphamide |
| publishDateSort |
2018 |
| publisher |
Wiley |
| recordtype |
ai |
| record_format |
ai |
| series |
International Journal of Cancer |
| source_id |
49 |
| title |
Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_unstemmed |
Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_full |
Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_fullStr |
Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_full_unstemmed |
Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_short |
Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_sort |
role of interferon regulatory factor 1 in governing <scp>t</scp>reg depletion, <scp>t</scp>h1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1002/ijc.31083 |
| publishDate |
2018 |
| physical |
976-987 |
| description |
<jats:p>The antitumor effectiveness of cyclophosphamide (CTX) and other chemotherapeutics was shown to rely not only on direct cytotoxicity but also on immunogenic tumor cell death and systemic immunomodulatory mechanisms, including regulatory T cell (Treg) depletion, Th1 cell polarization, type I interferon (IFN) and proinflammatory cytokine production. IFN regulatory factor (IRF)‐1 is a transcriptional regulator of IFNs and IFN‐inducible genes, involved in the control of Th1 and Treg differentiation and in sterile inflammation. Aim of this study was to explore the role of IRF‐1 in CTX‐induced antitumor effects and related immune activities. This study shows for the first time that IRF‐1 is important for the antitumor efficacy of CTX in mice. Moreover, experiments in tumor‐bearing C57BL/6 mice showed that <jats:italic>Irf1</jats:italic> gene expression in the spleen was transiently increased following CTX administration and correlated with the induction of Th1 cell expansion and of <jats:italic>Il12p40</jats:italic> gene expression, which is the main Th1‐driving cytokine. At the same time, CTX administration reduced both <jats:italic>Foxp3</jats:italic> expression and Treg cell percentages. These effects were abrogated in <jats:italic>Irf1<jats:sup>−/−</jats:sup></jats:italic> mice. Further experiments showed that the gene and/or protein expression of caspase‐1, iNOS, IL‐1β, IL‐6 and CXCL10 and the levels of nitric oxide were modulated following CTX in an IRF‐1‐direct‐ or ‐indirect‐dependent manner, and highlighted the importance of caspase‐1 in driving the sterile inflammatory response to CTX. Our data identify IRF‐1 as important for the antitumor efficacy of CTX and for the regulation of many immunomodulatory activities of CTX, such as Th1 polarization, Treg depletion and inflammation.</jats:p> |
| container_issue |
5 |
| container_start_page |
976 |
| container_title |
International Journal of Cancer |
| container_volume |
142 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792341994954031112 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T16:28:45.395Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Role+of+interferon+regulatory+factor+1+in+governing+Treg+depletion%2C+Th1+polarization%2C+inflammasome+activation+and+antitumor+efficacy+of+cyclophosphamide&rft.date=2018-03-01&genre=article&issn=1097-0215&volume=142&issue=5&spage=976&epage=987&pages=976-987&jtitle=International+Journal+of+Cancer&atitle=Role+of+interferon+regulatory+factor+1+in+governing+%3Cscp%3ET%3C%2Fscp%3Ereg+depletion%2C+%3Cscp%3ET%3C%2Fscp%3Eh1+polarization%2C+inflammasome+activation+and+antitumor+efficacy+of+cyclophosphamide&aulast=Moschella&aufirst=Federica&rft_id=info%3Adoi%2F10.1002%2Fijc.31083&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792341994954031112 |
| author | Buccione, Carla, Fragale, Alessandra, Polverino, Federica, Ziccheddu, Giovanna, Aricò, Eleonora, Belardelli, Filippo, Proietti, Enrico, Battistini, Angela, Moschella, Federica |
| author_facet | Buccione, Carla, Fragale, Alessandra, Polverino, Federica, Ziccheddu, Giovanna, Aricò, Eleonora, Belardelli, Filippo, Proietti, Enrico, Battistini, Angela, Moschella, Federica, Buccione, Carla, Fragale, Alessandra, Polverino, Federica, Ziccheddu, Giovanna, Aricò, Eleonora, Belardelli, Filippo, Proietti, Enrico, Battistini, Angela, Moschella, Federica |
| author_sort | buccione, carla |
| container_issue | 5 |
| container_start_page | 976 |
| container_title | International Journal of Cancer |
| container_volume | 142 |
| description | <jats:p>The antitumor effectiveness of cyclophosphamide (CTX) and other chemotherapeutics was shown to rely not only on direct cytotoxicity but also on immunogenic tumor cell death and systemic immunomodulatory mechanisms, including regulatory T cell (Treg) depletion, Th1 cell polarization, type I interferon (IFN) and proinflammatory cytokine production. IFN regulatory factor (IRF)‐1 is a transcriptional regulator of IFNs and IFN‐inducible genes, involved in the control of Th1 and Treg differentiation and in sterile inflammation. Aim of this study was to explore the role of IRF‐1 in CTX‐induced antitumor effects and related immune activities. This study shows for the first time that IRF‐1 is important for the antitumor efficacy of CTX in mice. Moreover, experiments in tumor‐bearing C57BL/6 mice showed that <jats:italic>Irf1</jats:italic> gene expression in the spleen was transiently increased following CTX administration and correlated with the induction of Th1 cell expansion and of <jats:italic>Il12p40</jats:italic> gene expression, which is the main Th1‐driving cytokine. At the same time, CTX administration reduced both <jats:italic>Foxp3</jats:italic> expression and Treg cell percentages. These effects were abrogated in <jats:italic>Irf1<jats:sup>−/−</jats:sup></jats:italic> mice. Further experiments showed that the gene and/or protein expression of caspase‐1, iNOS, IL‐1β, IL‐6 and CXCL10 and the levels of nitric oxide were modulated following CTX in an IRF‐1‐direct‐ or ‐indirect‐dependent manner, and highlighted the importance of caspase‐1 in driving the sterile inflammatory response to CTX. Our data identify IRF‐1 as important for the antitumor efficacy of CTX and for the regulation of many immunomodulatory activities of CTX, such as Th1 polarization, Treg depletion and inflammation.</jats:p> |
| doi_str_mv | 10.1002/ijc.31083 |
| facet_avail | Online, Free |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAwMi9pamMuMzEwODM |
| imprint | Wiley, 2018 |
| imprint_str_mv | Wiley, 2018 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
| issn | 0020-7136, 1097-0215 |
| issn_str_mv | 0020-7136, 1097-0215 |
| language | English |
| last_indexed | 2024-03-01T16:28:45.395Z |
| match_str | buccione2018roleofinterferonregulatoryfactor1ingoverningtregdepletionth1polarizationinflammasomeactivationandantitumorefficacyofcyclophosphamide |
| mega_collection | Wiley (CrossRef) |
| physical | 976-987 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | Wiley |
| record_format | ai |
| recordtype | ai |
| series | International Journal of Cancer |
| source_id | 49 |
| spelling | Buccione, Carla Fragale, Alessandra Polverino, Federica Ziccheddu, Giovanna Aricò, Eleonora Belardelli, Filippo Proietti, Enrico Battistini, Angela Moschella, Federica 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.31083 <jats:p>The antitumor effectiveness of cyclophosphamide (CTX) and other chemotherapeutics was shown to rely not only on direct cytotoxicity but also on immunogenic tumor cell death and systemic immunomodulatory mechanisms, including regulatory T cell (Treg) depletion, Th1 cell polarization, type I interferon (IFN) and proinflammatory cytokine production. IFN regulatory factor (IRF)‐1 is a transcriptional regulator of IFNs and IFN‐inducible genes, involved in the control of Th1 and Treg differentiation and in sterile inflammation. Aim of this study was to explore the role of IRF‐1 in CTX‐induced antitumor effects and related immune activities. This study shows for the first time that IRF‐1 is important for the antitumor efficacy of CTX in mice. Moreover, experiments in tumor‐bearing C57BL/6 mice showed that <jats:italic>Irf1</jats:italic> gene expression in the spleen was transiently increased following CTX administration and correlated with the induction of Th1 cell expansion and of <jats:italic>Il12p40</jats:italic> gene expression, which is the main Th1‐driving cytokine. At the same time, CTX administration reduced both <jats:italic>Foxp3</jats:italic> expression and Treg cell percentages. These effects were abrogated in <jats:italic>Irf1<jats:sup>−/−</jats:sup></jats:italic> mice. Further experiments showed that the gene and/or protein expression of caspase‐1, iNOS, IL‐1β, IL‐6 and CXCL10 and the levels of nitric oxide were modulated following CTX in an IRF‐1‐direct‐ or ‐indirect‐dependent manner, and highlighted the importance of caspase‐1 in driving the sterile inflammatory response to CTX. Our data identify IRF‐1 as important for the antitumor efficacy of CTX and for the regulation of many immunomodulatory activities of CTX, such as Th1 polarization, Treg depletion and inflammation.</jats:p> Role of interferon regulatory factor 1 in governing <scp>T</scp>reg depletion, <scp>T</scp>h1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide International Journal of Cancer |
| spellingShingle | Buccione, Carla, Fragale, Alessandra, Polverino, Federica, Ziccheddu, Giovanna, Aricò, Eleonora, Belardelli, Filippo, Proietti, Enrico, Battistini, Angela, Moschella, Federica, International Journal of Cancer, Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide, Cancer Research, Oncology |
| title | Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_full | Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_fullStr | Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_full_unstemmed | Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_short | Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_sort | role of interferon regulatory factor 1 in governing <scp>t</scp>reg depletion, <scp>t</scp>h1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| title_unstemmed | Role of interferon regulatory factor 1 in governing Treg depletion, Th1 polarization, inflammasome activation and antitumor efficacy of cyclophosphamide |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1002/ijc.31083 |