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Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy

Although photodynamic therapy (PDT) yields very good outcomes in numerous types of superficial solid cancers, some tumors respond suboptimally to PDT. Novel treatment strategies are therefore needed to enhance the efficacy in these therapy-resistant tumors. One of these strategies is to combine PDT...

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Autores principales: Broekgaarden, Mans, Kos, Milan, Jurg, Freek A., van Beek, Adriaan A., van Gulik, Thomas M., Heger, Michal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581334/
https://www.ncbi.nlm.nih.gov/pubmed/26307977
http://dx.doi.org/10.3390/ijms160819960
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author Broekgaarden, Mans
Kos, Milan
Jurg, Freek A.
van Beek, Adriaan A.
van Gulik, Thomas M.
Heger, Michal
author_facet Broekgaarden, Mans
Kos, Milan
Jurg, Freek A.
van Beek, Adriaan A.
van Gulik, Thomas M.
Heger, Michal
author_sort Broekgaarden, Mans
collection PubMed
description Although photodynamic therapy (PDT) yields very good outcomes in numerous types of superficial solid cancers, some tumors respond suboptimally to PDT. Novel treatment strategies are therefore needed to enhance the efficacy in these therapy-resistant tumors. One of these strategies is to combine PDT with inhibitors of PDT-induced survival pathways. In this respect, the transcription factor nuclear factor κB (NF-κB) has been identified as a potential pharmacological target, albeit inhibition of NF-κB may concurrently dampen the subsequent anti-tumor immune response required for complete tumor eradication and abscopal effects. In contrast to these postulations, this study demonstrated that siRNA knockdown of NF-κB in murine breast carcinoma (EMT-6) cells increased survival signaling in these cells and exacerbated the inflammatory response in murine RAW 264.7 macrophages. These results suggest a pro-death and immunosuppressive role of NF-κB in PDT-treated cells that concurs with a hyperstimulated immune response in innate immune cells.
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spelling pubmed-45813342015-09-28 Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy Broekgaarden, Mans Kos, Milan Jurg, Freek A. van Beek, Adriaan A. van Gulik, Thomas M. Heger, Michal Int J Mol Sci Article Although photodynamic therapy (PDT) yields very good outcomes in numerous types of superficial solid cancers, some tumors respond suboptimally to PDT. Novel treatment strategies are therefore needed to enhance the efficacy in these therapy-resistant tumors. One of these strategies is to combine PDT with inhibitors of PDT-induced survival pathways. In this respect, the transcription factor nuclear factor κB (NF-κB) has been identified as a potential pharmacological target, albeit inhibition of NF-κB may concurrently dampen the subsequent anti-tumor immune response required for complete tumor eradication and abscopal effects. In contrast to these postulations, this study demonstrated that siRNA knockdown of NF-κB in murine breast carcinoma (EMT-6) cells increased survival signaling in these cells and exacerbated the inflammatory response in murine RAW 264.7 macrophages. These results suggest a pro-death and immunosuppressive role of NF-κB in PDT-treated cells that concurs with a hyperstimulated immune response in innate immune cells. MDPI 2015-08-21 /pmc/articles/PMC4581334/ /pubmed/26307977 http://dx.doi.org/10.3390/ijms160819960 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Broekgaarden, Mans
Kos, Milan
Jurg, Freek A.
van Beek, Adriaan A.
van Gulik, Thomas M.
Heger, Michal
Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy
title Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy
title_full Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy
title_fullStr Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy
title_full_unstemmed Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy
title_short Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy
title_sort inhibition of nf-κb in tumor cells exacerbates immune cell activation following photodynamic therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581334/
https://www.ncbi.nlm.nih.gov/pubmed/26307977
http://dx.doi.org/10.3390/ijms160819960
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