Regulatory T Cell Inhibition by P60 Combined with Adenoviral AFP Transduced Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma
Regulatory T Cell Inhibition by P60 Combined with Adenoviral AFP Transduced Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma
Dokument öffnen (2.1MB)Datum der Veröffentlichung
17.10.2023Verlag / herausgebende Einrichtung
Taylor & FrancisVerlagsort
LondonMetadaten
Zur Langanzeige
Zitierbarer Link (Handle URI) 
https://hdl.handle.net/20.500.11811/13351
Inhalt
Background & Aims: Vaccination with tumor-associated antigen-pulsed dendritic cells leads to specific T-cell response against hepato-cellular carcinoma. However, clinical response has been shown to be limited. High regulatory T-cell count is associated with poor prognosis and seems to mediate immune tolerance in hepatocellular carcinoma. Forkhead box P3-peptide inhibitor P60 has been shown to specifically inhibit regulatory T-cell function in murine models. Aim of this study was to investigate whether P60 can improve the immune response induced by vaccination with adenovirus-transduced dendritic cells expressing alpha-fetoprotein in subcutaneous and orthotopic murine models for hepatocellular carcinoma.
Methods: Mice developing subcutaneous or orthotopic HCC received daily treatment with P60 starting at different tumor stages. Additionally, mice were vaccinated twice with dendritic cells expressing alpha-fetoprotein.
Results: In a preventive setting prior to tumor engraftment, vaccination with alpha-fetoprotein-expressing dendritic cells significantly decreased tumor growth in a subcutaneous model (p = .0256), but no further effects were achieved by addition of P60. However, P60 enhanced the antitumoral effect of a vaccination with alpha-fetoprotein-expressing dendritic cells in established subcutaneous and orthotopic hepatocellular carcinoma characterized by high Treg levels (p = .011).
Conclusion: In this study, we showed that vaccination with alpha-fetoprotein-expressing dendritic cells in combination with a specific inhibition of regulatory T-cells by using P60 leads to synergistic tumor inhibition and prolonged survival. This emphasizes the importance of regulatory T-cells inhibition for obtaining an effective antitumoral immune response in hepatocellular carcinoma.
Methods: Mice developing subcutaneous or orthotopic HCC received daily treatment with P60 starting at different tumor stages. Additionally, mice were vaccinated twice with dendritic cells expressing alpha-fetoprotein.
Results: In a preventive setting prior to tumor engraftment, vaccination with alpha-fetoprotein-expressing dendritic cells significantly decreased tumor growth in a subcutaneous model (p = .0256), but no further effects were achieved by addition of P60. However, P60 enhanced the antitumoral effect of a vaccination with alpha-fetoprotein-expressing dendritic cells in established subcutaneous and orthotopic hepatocellular carcinoma characterized by high Treg levels (p = .011).
Conclusion: In this study, we showed that vaccination with alpha-fetoprotein-expressing dendritic cells in combination with a specific inhibition of regulatory T-cells by using P60 leads to synergistic tumor inhibition and prolonged survival. This emphasizes the importance of regulatory T-cells inhibition for obtaining an effective antitumoral immune response in hepatocellular carcinoma.
Schlagwörter
Alpha-fetoprotein, cancer immunotherapy, dendritic cell-based vaccination, hepatocellular carcinoma, regulatory T-cells
Klassifikation (DDC)
610 Medizin, GesundheitErschienen in
Immunological Investigations, 2023, vol. 52, iss. 8, S. 966-984Erstpublikation
https://doi.org/10.1080/08820139.2023.2261980Sadeghlar, Farsaneh; Seelemann, Julia; Vogt, Annabelle; Möhring, Christian; Zhou, Taotao; Mahn, Robert; Kornek, Miroslaw; Lukacs-Kornek, Veronika; Casares, Noelia; Lasarte, Juan José; Sarobe, Pablo; Beekum, Cornelius van; Matthaei, Hanno; Manekeller, Steffen; Kalff, Jörg; Schmidt-Wolf, Ingo G.H.; Strassburg, Christian P.; Gonzalez-Carmona, Maria A.: Regulatory T Cell Inhibition by P60 Combined with Adenoviral AFP Transduced Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma. In: Immunological Investigations. 2023, vol. 52, iss. 8, 966-984.
Online-Ausgabe in bonndoc: https://hdl.handle.net/20.500.11811/13351
Online-Ausgabe in bonndoc: https://hdl.handle.net/20.500.11811/13351
@article{handle:20.500.11811/13351,
author = {{Farsaneh Sadeghlar} and {Julia Seelemann} and {Annabelle Vogt} and {Christian Möhring} and {Taotao Zhou} and {Robert Mahn} and {Miroslaw Kornek} and {Veronika Lukacs-Kornek} and {Noelia Casares} and {Juan José Lasarte} and {Pablo Sarobe} and {Cornelius van Beekum} and {Hanno Matthaei} and {Steffen Manekeller} and {Jörg Kalff} and {Ingo G.H. Schmidt-Wolf} and {Christian P. Strassburg} and {Maria A. Gonzalez-Carmona}},
title = {Regulatory T Cell Inhibition by P60 Combined with Adenoviral AFP Transduced Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma},
publisher = {Taylor & Francis},
year = 2023,
month = oct,
journal = {Immunological Investigations},
volume = 2023, vol. 52,
number = iss. 8,
pages = 966--984,
note = {Background & Aims: Vaccination with tumor-associated antigen-pulsed dendritic cells leads to specific T-cell response against hepato-cellular carcinoma. However, clinical response has been shown to be limited. High regulatory T-cell count is associated with poor prognosis and seems to mediate immune tolerance in hepatocellular carcinoma. Forkhead box P3-peptide inhibitor P60 has been shown to specifically inhibit regulatory T-cell function in murine models. Aim of this study was to investigate whether P60 can improve the immune response induced by vaccination with adenovirus-transduced dendritic cells expressing alpha-fetoprotein in subcutaneous and orthotopic murine models for hepatocellular carcinoma.
Methods: Mice developing subcutaneous or orthotopic HCC received daily treatment with P60 starting at different tumor stages. Additionally, mice were vaccinated twice with dendritic cells expressing alpha-fetoprotein.
Results: In a preventive setting prior to tumor engraftment, vaccination with alpha-fetoprotein-expressing dendritic cells significantly decreased tumor growth in a subcutaneous model (p = .0256), but no further effects were achieved by addition of P60. However, P60 enhanced the antitumoral effect of a vaccination with alpha-fetoprotein-expressing dendritic cells in established subcutaneous and orthotopic hepatocellular carcinoma characterized by high Treg levels (p = .011).
Conclusion: In this study, we showed that vaccination with alpha-fetoprotein-expressing dendritic cells in combination with a specific inhibition of regulatory T-cells by using P60 leads to synergistic tumor inhibition and prolonged survival. This emphasizes the importance of regulatory T-cells inhibition for obtaining an effective antitumoral immune response in hepatocellular carcinoma.},
url = {https://hdl.handle.net/20.500.11811/13351}
}
author = {{Farsaneh Sadeghlar} and {Julia Seelemann} and {Annabelle Vogt} and {Christian Möhring} and {Taotao Zhou} and {Robert Mahn} and {Miroslaw Kornek} and {Veronika Lukacs-Kornek} and {Noelia Casares} and {Juan José Lasarte} and {Pablo Sarobe} and {Cornelius van Beekum} and {Hanno Matthaei} and {Steffen Manekeller} and {Jörg Kalff} and {Ingo G.H. Schmidt-Wolf} and {Christian P. Strassburg} and {Maria A. Gonzalez-Carmona}},
title = {Regulatory T Cell Inhibition by P60 Combined with Adenoviral AFP Transduced Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma},
publisher = {Taylor & Francis},
year = 2023,
month = oct,
journal = {Immunological Investigations},
volume = 2023, vol. 52,
number = iss. 8,
pages = 966--984,
note = {Background & Aims: Vaccination with tumor-associated antigen-pulsed dendritic cells leads to specific T-cell response against hepato-cellular carcinoma. However, clinical response has been shown to be limited. High regulatory T-cell count is associated with poor prognosis and seems to mediate immune tolerance in hepatocellular carcinoma. Forkhead box P3-peptide inhibitor P60 has been shown to specifically inhibit regulatory T-cell function in murine models. Aim of this study was to investigate whether P60 can improve the immune response induced by vaccination with adenovirus-transduced dendritic cells expressing alpha-fetoprotein in subcutaneous and orthotopic murine models for hepatocellular carcinoma.
Methods: Mice developing subcutaneous or orthotopic HCC received daily treatment with P60 starting at different tumor stages. Additionally, mice were vaccinated twice with dendritic cells expressing alpha-fetoprotein.
Results: In a preventive setting prior to tumor engraftment, vaccination with alpha-fetoprotein-expressing dendritic cells significantly decreased tumor growth in a subcutaneous model (p = .0256), but no further effects were achieved by addition of P60. However, P60 enhanced the antitumoral effect of a vaccination with alpha-fetoprotein-expressing dendritic cells in established subcutaneous and orthotopic hepatocellular carcinoma characterized by high Treg levels (p = .011).
Conclusion: In this study, we showed that vaccination with alpha-fetoprotein-expressing dendritic cells in combination with a specific inhibition of regulatory T-cells by using P60 leads to synergistic tumor inhibition and prolonged survival. This emphasizes the importance of regulatory T-cells inhibition for obtaining an effective antitumoral immune response in hepatocellular carcinoma.},
url = {https://hdl.handle.net/20.500.11811/13351}
}
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