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Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade

BACKGROUND: Sub-lethal doses of ionizing radiation (IR) can alter the phenotype of target tissue by modulating genes that influence effector T cell activity. Previous studies indicate that cancer cells respond to radiation by up-regulating surface expression of death receptors, cell adhesion molecul...

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Autores principales: Kumari, Anita, Garnett-Benson, Charlie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752774/
https://www.ncbi.nlm.nih.gov/pubmed/26872462
http://dx.doi.org/10.1186/s13104-016-1914-9
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author Kumari, Anita
Garnett-Benson, Charlie
author_facet Kumari, Anita
Garnett-Benson, Charlie
author_sort Kumari, Anita
collection PubMed
description BACKGROUND: Sub-lethal doses of ionizing radiation (IR) can alter the phenotype of target tissue by modulating genes that influence effector T cell activity. Previous studies indicate that cancer cells respond to radiation by up-regulating surface expression of death receptors, cell adhesion molecules and tumor-associated antigens (TAA). However, there is limited information available regarding how T cells themselves are altered following these interactions with irradiated tumor cells. METHODS: Here, several human colorectal tumor cell lines were exposed to radiation (0–10 Gy) in vitro and changes in the expression of molecules costimulatory to effector T cells (4-1BBL, OX-40L, CD70, ICOSL) were examined by flow cytometry. T cell effector function was assessed to determine if changes in these proteins were directly related to the changes in T cell function. RESULTS: We found OX-40L and 4-1BBL to be the most consistently upregulated proteins on the surface of colorectal tumor cells post-IR while ICOSL and CD70 remained largely unaltered. Expression of these gene products correlated with enhanced killing of irradiated human colorectal tumor cells by TAA-specific T-cells. Importantly, blocking of both OX-40L and 4-1BBL reversed radiation-enhanced T-cell killing of human tumor targets as well as T-cell survival and activation. CONCLUSIONS: Overall, results of this study suggest that, beyond simply rendering tumor cells more sensitive to immune attack, radiation can be used to specifically modulate expression of genes that directly stimulate effector T cell activity.
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spelling pubmed-47527742016-02-14 Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade Kumari, Anita Garnett-Benson, Charlie BMC Res Notes Research Article BACKGROUND: Sub-lethal doses of ionizing radiation (IR) can alter the phenotype of target tissue by modulating genes that influence effector T cell activity. Previous studies indicate that cancer cells respond to radiation by up-regulating surface expression of death receptors, cell adhesion molecules and tumor-associated antigens (TAA). However, there is limited information available regarding how T cells themselves are altered following these interactions with irradiated tumor cells. METHODS: Here, several human colorectal tumor cell lines were exposed to radiation (0–10 Gy) in vitro and changes in the expression of molecules costimulatory to effector T cells (4-1BBL, OX-40L, CD70, ICOSL) were examined by flow cytometry. T cell effector function was assessed to determine if changes in these proteins were directly related to the changes in T cell function. RESULTS: We found OX-40L and 4-1BBL to be the most consistently upregulated proteins on the surface of colorectal tumor cells post-IR while ICOSL and CD70 remained largely unaltered. Expression of these gene products correlated with enhanced killing of irradiated human colorectal tumor cells by TAA-specific T-cells. Importantly, blocking of both OX-40L and 4-1BBL reversed radiation-enhanced T-cell killing of human tumor targets as well as T-cell survival and activation. CONCLUSIONS: Overall, results of this study suggest that, beyond simply rendering tumor cells more sensitive to immune attack, radiation can be used to specifically modulate expression of genes that directly stimulate effector T cell activity. BioMed Central 2016-02-13 /pmc/articles/PMC4752774/ /pubmed/26872462 http://dx.doi.org/10.1186/s13104-016-1914-9 Text en © Kumari and Garnett-Benson. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kumari, Anita
Garnett-Benson, Charlie
Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade
title Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade
title_full Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade
title_fullStr Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade
title_full_unstemmed Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade
title_short Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade
title_sort effector function of ctls is increased by irradiated colorectal tumor cells that modulate ox-40l and 4-1bbl and is reversed following dual blockade
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752774/
https://www.ncbi.nlm.nih.gov/pubmed/26872462
http://dx.doi.org/10.1186/s13104-016-1914-9
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