Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.

Radiation therapy aims to kill cancer cells with a minimum of normal tissue toxicity. Dying cancer cells have been proposed to be a source of tumor antigens and may release endogenous immune adjuvants into the tumor environment. For these reasons, radiation therapy may be an effective modality to in...

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Autores principales:	Marka R Crittenden, Benjamin Cottam, Talicia Savage, Cynthia Nguyen, Pippa Newell, Michael J Gough
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/97e5e31feaef4c54a3fffb274b2ef53f
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spelling	oai:doaj.org-article:97e5e31feaef4c54a3fffb274b2ef53f2021-11-18T07:14:08ZExpression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.1932-620310.1371/journal.pone.0039295https://doaj.org/article/97e5e31feaef4c54a3fffb274b2ef53f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761754/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Radiation therapy aims to kill cancer cells with a minimum of normal tissue toxicity. Dying cancer cells have been proposed to be a source of tumor antigens and may release endogenous immune adjuvants into the tumor environment. For these reasons, radiation therapy may be an effective modality to initiate new anti-tumor adaptive immune responses that can target residual disease and distant metastases. However, tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice, there is an influx of tumor macrophages that ultimately polarize towards immune suppression. We demonstrate using in vitro models that this polarization is mediated by transcriptional regulation by NFκB p50, and that in mice lacking NFκB p50, radiation therapy is more effective. We propose that despite the opportunity for increased antigen-specific adaptive immune responses, the intrinsic processes of repair following radiation therapy may limit the ability to control residual disease.Marka R CrittendenBenjamin CottamTalicia SavageCynthia NguyenPippa NewellMichael J GoughPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39295 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marka R Crittenden Benjamin Cottam Talicia Savage Cynthia Nguyen Pippa Newell Michael J Gough Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
description	Radiation therapy aims to kill cancer cells with a minimum of normal tissue toxicity. Dying cancer cells have been proposed to be a source of tumor antigens and may release endogenous immune adjuvants into the tumor environment. For these reasons, radiation therapy may be an effective modality to initiate new anti-tumor adaptive immune responses that can target residual disease and distant metastases. However, tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice, there is an influx of tumor macrophages that ultimately polarize towards immune suppression. We demonstrate using in vitro models that this polarization is mediated by transcriptional regulation by NFκB p50, and that in mice lacking NFκB p50, radiation therapy is more effective. We propose that despite the opportunity for increased antigen-specific adaptive immune responses, the intrinsic processes of repair following radiation therapy may limit the ability to control residual disease.
format	article
author	Marka R Crittenden Benjamin Cottam Talicia Savage Cynthia Nguyen Pippa Newell Michael J Gough
author_facet	Marka R Crittenden Benjamin Cottam Talicia Savage Cynthia Nguyen Pippa Newell Michael J Gough
author_sort	Marka R Crittenden
title	Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
title_short	Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
title_full	Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
title_fullStr	Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
title_full_unstemmed	Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
title_sort	expression of nf-κb p50 in tumor stroma limits the control of tumors by radiation therapy.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/97e5e31feaef4c54a3fffb274b2ef53f
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Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.

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