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Open AccessArticle

Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide

1
Department of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece
2
Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, NCSR “Demokritos”, Agia Paraskevi, 15310 Athens, Greece
3
King’s College London, Rayne Institute, 123 Coldharbour Lane, SE5 9NU London, UK
4
Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, 11527 Athens, Greece
5
Inflammation Research Group, Transgenic Technology Laboratory, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, 11521 Athens, Greece
6
Interfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen. Germany
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Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(11), 1764; https://doi.org/10.3390/cancers11111764
Received: 30 September 2019 / Revised: 4 November 2019 / Accepted: 6 November 2019 / Published: 9 November 2019
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. View Full-Text
Keywords: 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 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
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Birmpilis, A.I.; Karachaliou, C.-E.; Samara, P.; Ioannou, K.; Selemenakis, P.; Kostopoulos, I.V.; Kavrochorianou, N.; Kalbacher, H.; Livaniou, E.; Haralambous, S.; Kotsinas, A.; Farzaneh, F.; Trougakos, I.P.; Voelter, W.; Dimopoulos, M.-A.; Bamias, A.; Tsitsilonis, O. Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide. Cancers 2019, 11, 1764.

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