Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide
Prothymosin α (proTα) and its C-terminal decapeptide proTα(100−109) were shown to pleiotropically enhance innate and adaptive immune responses. Their activities have been broadly studied in vitro, focusing primarily on the restoration of the deficient immunoreact...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/11/1764 |
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doaj-0334bad1cb654a95b70a9400584d91c5 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Anastasios I. Birmpilis Chrysoula-Evangelia Karachaliou Pinelopi Samara Kyriaki Ioannou Platon Selemenakis Ioannis V. Kostopoulos Nadia Kavrochorianou Hubert Kalbacher Evangelia Livaniou Sylva Haralambous Athanasios Kotsinas Farzin Farzaneh Ioannis P. Trougakos Wolfgang Voelter Meletios-Athanasios Dimopoulos Aristotelis Bamias Ourania Tsitsilonis |
| spellingShingle |
Anastasios I. Birmpilis Chrysoula-Evangelia Karachaliou Pinelopi Samara Kyriaki Ioannou Platon Selemenakis Ioannis V. Kostopoulos Nadia Kavrochorianou Hubert Kalbacher Evangelia Livaniou Sylva Haralambous Athanasios Kotsinas Farzin Farzaneh Ioannis P. Trougakos Wolfgang Voelter Meletios-Athanasios Dimopoulos Aristotelis Bamias Ourania Tsitsilonis Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide Cancers adjuvant antitumor peptide vaccine biologic response modifier danger-associated molecular pattern—damp immunoreactive decapeptide in vivo melanoma model proinflammatory cytokine prothymosin α th1-type cytokine |
| author_facet |
Anastasios I. Birmpilis Chrysoula-Evangelia Karachaliou Pinelopi Samara Kyriaki Ioannou Platon Selemenakis Ioannis V. Kostopoulos Nadia Kavrochorianou Hubert Kalbacher Evangelia Livaniou Sylva Haralambous Athanasios Kotsinas Farzin Farzaneh Ioannis P. Trougakos Wolfgang Voelter Meletios-Athanasios Dimopoulos Aristotelis Bamias Ourania Tsitsilonis |
| author_sort |
Anastasios I. Birmpilis |
| title |
Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide |
| title_short |
Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide |
| title_full |
Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide |
| title_fullStr |
Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide |
| title_full_unstemmed |
Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide |
| title_sort |
antitumor reactive t-cell responses are enhanced in vivo by damp prothymosin alpha and its c-terminal decapeptide |
| publisher |
MDPI AG |
| series |
Cancers |
| issn |
2072-6694 |
| publishDate |
2019-11-01 |
| description |
Prothymosin α (proTα) and its C-terminal decapeptide proTα(100−109) were shown to pleiotropically enhance innate and adaptive immune responses. Their activities have been broadly studied in vitro, focusing primarily on the restoration of the deficient immunoreactivity of cancer patients’ leukocytes. Previously, we showed that proTα and proTα(100−109) act as danger-associated molecular patterns (DAMPs), ligate Toll-like receptor-4, signal through TRIF- and MyD88-dependent pathways, promote the maturation of dendritic cells and elicit T-helper type 1 (Th1) immune responses in vitro, leading to the optimal priming of tumor antigen-reactive T-cell functions. Herein, we assessed their activity in a preclinical melanoma model. Immunocompetent mice bearing B16.F1 tumors were treated with two cycles of proTα or proTα(100−109) together with a B16.F1-derived peptide vaccine. Coadministration of proTα or proTα(100−109) and the peptide vaccine suppressed melanoma-cell proliferation, as evidenced by reduced tumor-growth rates. Higher melanoma infiltration by CD3+ T cells was observed, whereas ex vivo analysis of mouse total spleen cells verified the in vivo induction of melanoma-reactive cytotoxic responses. Additionally, increased levels of proinflammatory and Th1-type cytokines were detected in mouse serum. We propose that, in the presence of tumor antigens, DAMPs proTα and proTα(100−109) induce Th1-biased immune responses in vivo. Their adjuvant ability to orchestrate antitumor immunoreactivities can eventually be exploited therapeutically in humans. |
| topic |
adjuvant antitumor peptide vaccine biologic response modifier danger-associated molecular pattern—damp immunoreactive decapeptide in vivo melanoma model proinflammatory cytokine prothymosin α th1-type cytokine |
| url |
https://www.mdpi.com/2072-6694/11/11/1764 |
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doaj-0334bad1cb654a95b70a9400584d91c52020-11-25T01:35:03ZengMDPI AGCancers2072-66942019-11-011111176410.3390/cancers11111764cancers11111764Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal DecapeptideAnastasios I. Birmpilis0Chrysoula-Evangelia Karachaliou1Pinelopi Samara2Kyriaki Ioannou3Platon Selemenakis4Ioannis V. Kostopoulos5Nadia Kavrochorianou6Hubert Kalbacher7Evangelia Livaniou8Sylva Haralambous9Athanasios Kotsinas10Farzin Farzaneh11Ioannis P. Trougakos12Wolfgang Voelter13Meletios-Athanasios Dimopoulos14Aristotelis Bamias15Ourania Tsitsilonis16Department of Biology, National and Kapodistrian University of Athens, 15784 Athens, GreeceInstitute of Nuclear and Radiological Sciences and Technology, Energy and Safety, NCSR “Demokritos”, Agia Paraskevi, 15310 Athens, GreeceDepartment of Biology, National and Kapodistrian University of Athens, 15784 Athens, GreeceDepartment of Biology, National and Kapodistrian University of Athens, 15784 Athens, GreeceMolecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, 11527 Athens, GreeceDepartment of Biology, National and Kapodistrian University of Athens, 15784 Athens, GreeceInflammation Research Group, Transgenic Technology Laboratory, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, 11521 Athens, GreeceInterfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen. GermanyInstitute of Nuclear and Radiological Sciences and Technology, Energy and Safety, NCSR “Demokritos”, Agia Paraskevi, 15310 Athens, GreeceInflammation Research Group, Transgenic Technology Laboratory, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, 11521 Athens, GreeceMolecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, 11527 Athens, GreeceKing’s College London, Rayne Institute, 123 Coldharbour Lane, SE5 9NU London, UKDepartment of Biology, National and Kapodistrian University of Athens, 15784 Athens, GreeceInterfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen. GermanyDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Biology, National and Kapodistrian University of Athens, 15784 Athens, GreeceProthymosin α (proTα) and its C-terminal decapeptide proTα(100−109) were shown to pleiotropically enhance innate and adaptive immune responses. Their activities have been broadly studied in vitro, focusing primarily on the restoration of the deficient immunoreactivity of cancer patients’ leukocytes. Previously, we showed that proTα and proTα(100−109) act as danger-associated molecular patterns (DAMPs), ligate Toll-like receptor-4, signal through TRIF- and MyD88-dependent pathways, promote the maturation of dendritic cells and elicit T-helper type 1 (Th1) immune responses in vitro, leading to the optimal priming of tumor antigen-reactive T-cell functions. Herein, we assessed their activity in a preclinical melanoma model. Immunocompetent mice bearing B16.F1 tumors were treated with two cycles of proTα or proTα(100−109) together with a B16.F1-derived peptide vaccine. Coadministration of proTα or proTα(100−109) and the peptide vaccine suppressed melanoma-cell proliferation, as evidenced by reduced tumor-growth rates. Higher melanoma infiltration by CD3+ T cells was observed, whereas ex vivo analysis of mouse total spleen cells verified the in vivo induction of melanoma-reactive cytotoxic responses. Additionally, increased levels of proinflammatory and Th1-type cytokines were detected in mouse serum. We propose that, in the presence of tumor antigens, DAMPs proTα and proTα(100−109) induce Th1-biased immune responses in vivo. Their adjuvant ability to orchestrate antitumor immunoreactivities can eventually be exploited therapeutically in humans.https://www.mdpi.com/2072-6694/11/11/1764adjuvantantitumor peptide vaccinebiologic response modifierdanger-associated molecular pattern—dampimmunoreactive decapeptidein vivo melanoma modelproinflammatory cytokineprothymosin αth1-type cytokine |