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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 immunoreactivity of cancer patients’ leukocytes....
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896021/ https://www.ncbi.nlm.nih.gov/pubmed/31717548 http://dx.doi.org/10.3390/cancers11111764 |
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author | Birmpilis, Anastasios I. Karachaliou, Chrysoula-Evangelia Samara, Pinelopi Ioannou, Kyriaki Selemenakis, Platon Kostopoulos, Ioannis V. Kavrochorianou, Nadia Kalbacher, Hubert Livaniou, Evangelia Haralambous, Sylva Kotsinas, Athanasios Farzaneh, Farzin Trougakos, Ioannis P. Voelter, Wolfgang Dimopoulos, Meletios-Athanasios Bamias, Aristotelis Tsitsilonis, Ourania |
author_facet | Birmpilis, Anastasios I. Karachaliou, Chrysoula-Evangelia Samara, Pinelopi Ioannou, Kyriaki Selemenakis, Platon Kostopoulos, Ioannis V. Kavrochorianou, Nadia Kalbacher, Hubert Livaniou, Evangelia Haralambous, Sylva Kotsinas, Athanasios Farzaneh, Farzin Trougakos, Ioannis P. Voelter, Wolfgang Dimopoulos, Meletios-Athanasios Bamias, Aristotelis Tsitsilonis, Ourania |
author_sort | Birmpilis, Anastasios I. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6896021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68960212019-12-24 Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide Birmpilis, Anastasios I. Karachaliou, Chrysoula-Evangelia Samara, Pinelopi Ioannou, Kyriaki Selemenakis, Platon Kostopoulos, Ioannis V. Kavrochorianou, Nadia Kalbacher, Hubert Livaniou, Evangelia Haralambous, Sylva Kotsinas, Athanasios Farzaneh, Farzin Trougakos, Ioannis P. Voelter, Wolfgang Dimopoulos, Meletios-Athanasios Bamias, Aristotelis Tsitsilonis, Ourania Cancers (Basel) Article 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. MDPI 2019-11-09 /pmc/articles/PMC6896021/ /pubmed/31717548 http://dx.doi.org/10.3390/cancers11111764 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Birmpilis, Anastasios I. Karachaliou, Chrysoula-Evangelia Samara, Pinelopi Ioannou, Kyriaki Selemenakis, Platon Kostopoulos, Ioannis V. Kavrochorianou, Nadia Kalbacher, Hubert Livaniou, Evangelia Haralambous, Sylva Kotsinas, Athanasios Farzaneh, Farzin Trougakos, Ioannis P. Voelter, Wolfgang Dimopoulos, Meletios-Athanasios Bamias, Aristotelis Tsitsilonis, Ourania Antitumor Reactive T-Cell Responses Are Enhanced In Vivo by DAMP Prothymosin Alpha and Its C-Terminal Decapeptide |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896021/ https://www.ncbi.nlm.nih.gov/pubmed/31717548 http://dx.doi.org/10.3390/cancers11111764 |
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