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Dendritic cells loaded with exosomes derived from cancer stem cell‐enriched spheroids as a potential immunotherapeutic option

Cancer stem cells (CSCs) are responsible for therapeutic resistance and recurrence in colorectal cancer. Despite advances in immunotherapy, the inability to specifically eradicate CSCs has led to treatment failure. Hence, identification of appropriate antigen sources is a major challenge in designin...

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Autores principales: Naseri, Marzieh, Zöller, Margot, Hadjati, Jamshid, Ghods, Roya, Ranaei Pirmardan, Ehsan, Kiani, Jafar, Eini, Leila, Bozorgmehr, Mahmood, Madjd, Zahra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034455/
https://www.ncbi.nlm.nih.gov/pubmed/33634564
http://dx.doi.org/10.1111/jcmm.16401
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author Naseri, Marzieh
Zöller, Margot
Hadjati, Jamshid
Ghods, Roya
Ranaei Pirmardan, Ehsan
Kiani, Jafar
Eini, Leila
Bozorgmehr, Mahmood
Madjd, Zahra
author_facet Naseri, Marzieh
Zöller, Margot
Hadjati, Jamshid
Ghods, Roya
Ranaei Pirmardan, Ehsan
Kiani, Jafar
Eini, Leila
Bozorgmehr, Mahmood
Madjd, Zahra
author_sort Naseri, Marzieh
collection PubMed
description Cancer stem cells (CSCs) are responsible for therapeutic resistance and recurrence in colorectal cancer. Despite advances in immunotherapy, the inability to specifically eradicate CSCs has led to treatment failure. Hence, identification of appropriate antigen sources is a major challenge in designing dendritic cell (DC)‐based therapeutic strategies against CSCs. Here, in an in vitro model using the HT‐29 colon cancer cell line, we explored the efficacy of DCs loaded with exosomes derived from CSC‐enriched colonospheres (CSC(enr)‐EXOs) as an antigen source in activating CSC‐specific T‐cell responses. HT‐29 lysate, HT‐29‐EXOs and CSC(enr) lysate were independently assessed as separate antigen sources. Having confirmed CSCs enrichment in spheroids, CSC(enr)‐EXOs were purified and characterized, and their impact on DC maturation was investigated. Finally, the impact of the antigen‐pulsed DCs on the proliferation rate and also spheroid destructive capacity of autologous T cells was assessed. CSC(enr)‐EXOs similar to other antigen groups had no suppressive/negative impacts on phenotypic maturation of DCs as judged by the expression level of costimulatory molecules. Notably, similar to CSC(enr) lysate, CSC(enr)‐EXOs significantly increased the IL‐12/IL‐10 ratio in supernatants of mature DCs. CSC(enr)‐EXO‐loaded DCs effectively promoted T‐cell proliferation. Importantly, T cells stimulated with CSC(enr)‐EXOs disrupted spheroids' structure. Thus, CSC(enr)‐EXOs present a novel and promising antigen source that in combination with conventional tumour bulk‐derived antigens should be further explored in pre‐clinical immunotherapeutic settings for the efficacy in hampering recurrence and metastatic spread.
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spelling pubmed-80344552021-04-14 Dendritic cells loaded with exosomes derived from cancer stem cell‐enriched spheroids as a potential immunotherapeutic option Naseri, Marzieh Zöller, Margot Hadjati, Jamshid Ghods, Roya Ranaei Pirmardan, Ehsan Kiani, Jafar Eini, Leila Bozorgmehr, Mahmood Madjd, Zahra J Cell Mol Med Original Articles Cancer stem cells (CSCs) are responsible for therapeutic resistance and recurrence in colorectal cancer. Despite advances in immunotherapy, the inability to specifically eradicate CSCs has led to treatment failure. Hence, identification of appropriate antigen sources is a major challenge in designing dendritic cell (DC)‐based therapeutic strategies against CSCs. Here, in an in vitro model using the HT‐29 colon cancer cell line, we explored the efficacy of DCs loaded with exosomes derived from CSC‐enriched colonospheres (CSC(enr)‐EXOs) as an antigen source in activating CSC‐specific T‐cell responses. HT‐29 lysate, HT‐29‐EXOs and CSC(enr) lysate were independently assessed as separate antigen sources. Having confirmed CSCs enrichment in spheroids, CSC(enr)‐EXOs were purified and characterized, and their impact on DC maturation was investigated. Finally, the impact of the antigen‐pulsed DCs on the proliferation rate and also spheroid destructive capacity of autologous T cells was assessed. CSC(enr)‐EXOs similar to other antigen groups had no suppressive/negative impacts on phenotypic maturation of DCs as judged by the expression level of costimulatory molecules. Notably, similar to CSC(enr) lysate, CSC(enr)‐EXOs significantly increased the IL‐12/IL‐10 ratio in supernatants of mature DCs. CSC(enr)‐EXO‐loaded DCs effectively promoted T‐cell proliferation. Importantly, T cells stimulated with CSC(enr)‐EXOs disrupted spheroids' structure. Thus, CSC(enr)‐EXOs present a novel and promising antigen source that in combination with conventional tumour bulk‐derived antigens should be further explored in pre‐clinical immunotherapeutic settings for the efficacy in hampering recurrence and metastatic spread. John Wiley and Sons Inc. 2021-02-25 2021-04 /pmc/articles/PMC8034455/ /pubmed/33634564 http://dx.doi.org/10.1111/jcmm.16401 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Naseri, Marzieh
Zöller, Margot
Hadjati, Jamshid
Ghods, Roya
Ranaei Pirmardan, Ehsan
Kiani, Jafar
Eini, Leila
Bozorgmehr, Mahmood
Madjd, Zahra
Dendritic cells loaded with exosomes derived from cancer stem cell‐enriched spheroids as a potential immunotherapeutic option
title Dendritic cells loaded with exosomes derived from cancer stem cell‐enriched spheroids as a potential immunotherapeutic option
title_full Dendritic cells loaded with exosomes derived from cancer stem cell‐enriched spheroids as a potential immunotherapeutic option
title_fullStr Dendritic cells loaded with exosomes derived from cancer stem cell‐enriched spheroids as a potential immunotherapeutic option
title_full_unstemmed Dendritic cells loaded with exosomes derived from cancer stem cell‐enriched spheroids as a potential immunotherapeutic option
title_short Dendritic cells loaded with exosomes derived from cancer stem cell‐enriched spheroids as a potential immunotherapeutic option
title_sort dendritic cells loaded with exosomes derived from cancer stem cell‐enriched spheroids as a potential immunotherapeutic option
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034455/
https://www.ncbi.nlm.nih.gov/pubmed/33634564
http://dx.doi.org/10.1111/jcmm.16401
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