title: Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy.
abstract: 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.
authors: Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. mbroekgaarden@mgh.harvard.edu.
authors: Mans
authors: M
authors: Broekgaarden
authors: Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. milan.kos@amc.uva.nl.
authors: Milan
authors: M
authors: Kos
authors: Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. freek@moonshots.nl.
authors: Freek A
authors: FA
authors: Jurg
authors: Department of Cell Biology and Immunology, Wageningen University, 6709 PG Wageningen, The Netherlands. adriaan.vanbeek@wur.nl.
authors: Adriaan A
authors: AA
authors: van Beek
authors: Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. t.m.vangulik@amc.uva.nl.
authors: Thomas M
authors: TM
authors: van Gulik
authors: Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. m.heger@amc.uva.nl.
authors: Michal
authors: M
authors: Heger
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D055785:Gene Knockdown Techniques; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009942:Organometallic Compounds / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D017967:Zinc Compounds
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D007211:Indoles; D054833:Isoindoles; D016328:NF-kappa B; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D034741:RNA, Small Interfering; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine
keywords: anti-tumor immunity; inflammation; interferon gamma; interleukin-12p70; interleukin-6; monocyte chemotactic protein 1 interleukin-10; phototherapy; siRNA; tumor necrosis factor alpha