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

International Journal of Molecular Sciences

Mans Broekgaarden³  Milan Kos³  Freek A. Jurg³  Adriaan A. van Beek¹  Thomas M. van Gulik³  Michal Heger³  Michael R. Hamblin² 

[1] Department of Cell Biology and Immunology, Wageningen University, 6709 PG Wageningen, The Netherlands; E-Mail:Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;;Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; E-Mails:

关键词: phototherapy;    inflammation;    anti-tumor immunity;    siRNA;    interleukin-6;    tumor necrosis factor alpha;    monocyte chemotactic protein 1 interleukin-10;    interleukin-12p70;    interferon gamma;   

DOI  :  10.3390/ijms160819960

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.