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The anticancer peptide RT53 induces immunogenic cell death

In recent years, immunogenic cell death (ICD) has emerged as a revolutionary concept in the development of novel anticancer therapies. This particular form of cell death is able, through the spatiotemporally defined emission of danger signals by the dying cell, to induce an effective antitumor immun...

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Autores principales: Pasquereau-Kotula, Ewa, Habault, Justine, Kroemer, Guido, Poyet, Jean-Luc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078289/
https://www.ncbi.nlm.nih.gov/pubmed/30080874
http://dx.doi.org/10.1371/journal.pone.0201220
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author Pasquereau-Kotula, Ewa
Habault, Justine
Kroemer, Guido
Poyet, Jean-Luc
author_facet Pasquereau-Kotula, Ewa
Habault, Justine
Kroemer, Guido
Poyet, Jean-Luc
author_sort Pasquereau-Kotula, Ewa
collection PubMed
description In recent years, immunogenic cell death (ICD) has emerged as a revolutionary concept in the development of novel anticancer therapies. This particular form of cell death is able, through the spatiotemporally defined emission of danger signals by the dying cell, to induce an effective antitumor immune response, allowing the immune system to recognize and eradicate malignant cells. To date, only a restricted number of chemotherapeutics can trigger ICD of cancer cells. We previously reported that a peptide, called RT53, spanning the heptad leucine repeat region of the survival protein AAC-11 fused to a penetrating sequence, selectively induces cancer cell death in vitro and in vivo. Interestingly, B16F10 melanoma cells treated by RT53 were able to mediate anticancer effects in a tumor vaccination model. Stimulated by this observation, we investigated whether RT53 might mediate ICD of cancer cells. Here, we report that RT53 treatment induces all the hallmarks of immunogenic cell death, as defined by the plasma membrane exposure of calreticulin, release of ATP and the exodus of high-mobility group box 1 protein (HMGB1) from dying cancer cells, through a non-regulated, membranolytic mode of action. In a prophylactic mouse model, vaccination with RT53-treated fibrosarcomas prevented tumor growth at the challenge site. Finally, local intratumoral injection of RT53 into established cancers led to tumor regression together with T-cell infiltration and the mounting of an inflammatory response in the treated animals. Collectively, our results strongly suggest that RT53 can induce bona fide ICD of cancer cells and illustrate its potential use as a novel antitumor and immunotherapeutic strategy.
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spelling pubmed-60782892018-08-28 The anticancer peptide RT53 induces immunogenic cell death Pasquereau-Kotula, Ewa Habault, Justine Kroemer, Guido Poyet, Jean-Luc PLoS One Research Article In recent years, immunogenic cell death (ICD) has emerged as a revolutionary concept in the development of novel anticancer therapies. This particular form of cell death is able, through the spatiotemporally defined emission of danger signals by the dying cell, to induce an effective antitumor immune response, allowing the immune system to recognize and eradicate malignant cells. To date, only a restricted number of chemotherapeutics can trigger ICD of cancer cells. We previously reported that a peptide, called RT53, spanning the heptad leucine repeat region of the survival protein AAC-11 fused to a penetrating sequence, selectively induces cancer cell death in vitro and in vivo. Interestingly, B16F10 melanoma cells treated by RT53 were able to mediate anticancer effects in a tumor vaccination model. Stimulated by this observation, we investigated whether RT53 might mediate ICD of cancer cells. Here, we report that RT53 treatment induces all the hallmarks of immunogenic cell death, as defined by the plasma membrane exposure of calreticulin, release of ATP and the exodus of high-mobility group box 1 protein (HMGB1) from dying cancer cells, through a non-regulated, membranolytic mode of action. In a prophylactic mouse model, vaccination with RT53-treated fibrosarcomas prevented tumor growth at the challenge site. Finally, local intratumoral injection of RT53 into established cancers led to tumor regression together with T-cell infiltration and the mounting of an inflammatory response in the treated animals. Collectively, our results strongly suggest that RT53 can induce bona fide ICD of cancer cells and illustrate its potential use as a novel antitumor and immunotherapeutic strategy. Public Library of Science 2018-08-06 /pmc/articles/PMC6078289/ /pubmed/30080874 http://dx.doi.org/10.1371/journal.pone.0201220 Text en © 2018 Pasquereau-Kotula et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pasquereau-Kotula, Ewa
Habault, Justine
Kroemer, Guido
Poyet, Jean-Luc
The anticancer peptide RT53 induces immunogenic cell death
title The anticancer peptide RT53 induces immunogenic cell death
title_full The anticancer peptide RT53 induces immunogenic cell death
title_fullStr The anticancer peptide RT53 induces immunogenic cell death
title_full_unstemmed The anticancer peptide RT53 induces immunogenic cell death
title_short The anticancer peptide RT53 induces immunogenic cell death
title_sort anticancer peptide rt53 induces immunogenic cell death
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078289/
https://www.ncbi.nlm.nih.gov/pubmed/30080874
http://dx.doi.org/10.1371/journal.pone.0201220
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