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Simulated microgravity-mediated reversion of murine lymphoma immune evasion

No human has returned to the moon since the end of the Apollo program 47 years ago, however, new missions are planned for an orbital outpost. Space radiation and the potential for cancer remain as important issues to the future of human space exploration. While improved shield technologies and prote...

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Autores principales: Bradley, Jillian H., Barwick, Shannon, Horn, Gillian Q., Ullrich, Elizabeth, Best, Brianna, Arnold, Jennifer P., Gregg, Randal K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787044/
https://www.ncbi.nlm.nih.gov/pubmed/31602007
http://dx.doi.org/10.1038/s41598-019-51106-y
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author Bradley, Jillian H.
Barwick, Shannon
Horn, Gillian Q.
Ullrich, Elizabeth
Best, Brianna
Arnold, Jennifer P.
Gregg, Randal K.
author_facet Bradley, Jillian H.
Barwick, Shannon
Horn, Gillian Q.
Ullrich, Elizabeth
Best, Brianna
Arnold, Jennifer P.
Gregg, Randal K.
author_sort Bradley, Jillian H.
collection PubMed
description No human has returned to the moon since the end of the Apollo program 47 years ago, however, new missions are planned for an orbital outpost. Space radiation and the potential for cancer remain as important issues to the future of human space exploration. While improved shield technologies and protective biologicals are under development, little is known concerning the interaction between cancer cells and host immunity in microgravity. As a hallmark of cancer, tumor cells employ mechanisms of immune evasion to avoid elimination by protective CD4(+) and CD8(+) T cells. We showed that a murine lymphoma was able to produce a soluble factor that inhibited the function of dendritic cells in activating the CD4(+) T cells. Culture of the lymphoma cells in simulated microgravity (SMG), and not Static conditions, restored the CD4(+) T cell response and augmented CD8(+) T cell-mediated destruction of the cancer cells in vitro and in vivo. Thus, SMG impaired the mechanism of tumor escape and rendered the cancer cells more susceptible to T cell-mediated elimination. The stress of microgravity may expose the most critical components of a tumor’s escape mechanism for astronaut protection and the generation of new cancer therapeutics for patients on Earth.
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spelling pubmed-67870442019-10-17 Simulated microgravity-mediated reversion of murine lymphoma immune evasion Bradley, Jillian H. Barwick, Shannon Horn, Gillian Q. Ullrich, Elizabeth Best, Brianna Arnold, Jennifer P. Gregg, Randal K. Sci Rep Article No human has returned to the moon since the end of the Apollo program 47 years ago, however, new missions are planned for an orbital outpost. Space radiation and the potential for cancer remain as important issues to the future of human space exploration. While improved shield technologies and protective biologicals are under development, little is known concerning the interaction between cancer cells and host immunity in microgravity. As a hallmark of cancer, tumor cells employ mechanisms of immune evasion to avoid elimination by protective CD4(+) and CD8(+) T cells. We showed that a murine lymphoma was able to produce a soluble factor that inhibited the function of dendritic cells in activating the CD4(+) T cells. Culture of the lymphoma cells in simulated microgravity (SMG), and not Static conditions, restored the CD4(+) T cell response and augmented CD8(+) T cell-mediated destruction of the cancer cells in vitro and in vivo. Thus, SMG impaired the mechanism of tumor escape and rendered the cancer cells more susceptible to T cell-mediated elimination. The stress of microgravity may expose the most critical components of a tumor’s escape mechanism for astronaut protection and the generation of new cancer therapeutics for patients on Earth. Nature Publishing Group UK 2019-10-10 /pmc/articles/PMC6787044/ /pubmed/31602007 http://dx.doi.org/10.1038/s41598-019-51106-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Bradley, Jillian H.
Barwick, Shannon
Horn, Gillian Q.
Ullrich, Elizabeth
Best, Brianna
Arnold, Jennifer P.
Gregg, Randal K.
Simulated microgravity-mediated reversion of murine lymphoma immune evasion
title Simulated microgravity-mediated reversion of murine lymphoma immune evasion
title_full Simulated microgravity-mediated reversion of murine lymphoma immune evasion
title_fullStr Simulated microgravity-mediated reversion of murine lymphoma immune evasion
title_full_unstemmed Simulated microgravity-mediated reversion of murine lymphoma immune evasion
title_short Simulated microgravity-mediated reversion of murine lymphoma immune evasion
title_sort simulated microgravity-mediated reversion of murine lymphoma immune evasion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787044/
https://www.ncbi.nlm.nih.gov/pubmed/31602007
http://dx.doi.org/10.1038/s41598-019-51106-y
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