Maria Margarete Karsten1, Sabine Enders2, Julia Knabl2, Verena Kirn3, Peter Düwell4, Brigitte Rack2, Jens-Uwe Blohmer5, Doris Mayr6, Darius Dian2. 1. Klinik für Gynäkologie und Brustzentrum, Charité Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Germany. maria-margarete.karsten@charite.de. 2. Klinik für Frauenheilkunde, Ludwig-Maximilians-Universität München, Munich, Germany. 3. Klinik und Poliklinik für Frauenheilkunde, Universität Köln, Cologne, Germany. 4. Abteilung für klinische Pharmakologie, Ludwig-Maximilians-Universität München, Munich, Germany. 5. Klinik für Gynäkologie und Brustzentrum, Charité Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Germany. 6. Abteilung für Pathologie, Ludwig-Maximilians-Universität München, Munich, Germany.
Abstract
PURPOSE: In 2005, Breuing et al. first described the use of acellular dermal matrices (ADMs) in breast cancer patients. ADMs are assumed to be safe to use in an oncologic setting, but data from controlled studies are still needed. Here, we investigate the effects of ADMs on the production of interleukin (IL)-6 and IL-12, key regulators of immune suppression and activation. METHODS: Strattice (ST), CollaMend (CM), and Biodesign (BD) biologic meshes and TiLoop, a synthetic mesh (TL), were used in this study. We isolated myeloid dendritic cells (MDCs), untouched plasmacytoid dendritic cells (pDCs), naïve B cells, and CD8+ T cells and co-cultured these cells with either the biologic meshes or TL. As positive controls, we used CpG ODN 2216 or lipopolysaccharide (LPS). The cytokine concentrations of IL-12p70 and IL-6 were determined after 7 days using sandwich ELISA sets. RESULTS: There were highly significant differences between the ADMs and TL in terms of their ability to stimulate immunologic responses. IL-6 expression was significantly increased in B cells (p = 0.0006131) and T cells (p = 0.00418) when comparing TL and ADMs. We also identified significant differences in IL-12 production by B cells (p = 0.0166) and T cells (p = 0.003636) when comparing TL and ADMs. CONCLUSIONS: Despite the assumed lack of an immunological response to ADMs, in our experimental study, human immune cells reacted with significantly different cytokine profiles. These findings may have implications for the potential activation or suppression of effector cells in cancer patients and could explain some of the post clinical post surgical signs of ADMS like skin rush and seroma.
PURPOSE: In 2005, Breuing et al. first described the use of acellular dermal matrices (ADMs) in breast cancerpatients. ADMs are assumed to be safe to use in an oncologic setting, but data from controlled studies are still needed. Here, we investigate the effects of ADMs on the production of interleukin (IL)-6 and IL-12, key regulators of immune suppression and activation. METHODS: Strattice (ST), CollaMend (CM), and Biodesign (BD) biologic meshes and TiLoop, a synthetic mesh (TL), were used in this study. We isolated myeloid dendritic cells (MDCs), untouched plasmacytoid dendritic cells (pDCs), naïve B cells, and CD8+ T cells and co-cultured these cells with either the biologic meshes or TL. As positive controls, we used CpG ODN 2216 or lipopolysaccharide (LPS). The cytokine concentrations of IL-12p70 and IL-6 were determined after 7 days using sandwich ELISA sets. RESULTS: There were highly significant differences between the ADMs and TL in terms of their ability to stimulate immunologic responses. IL-6 expression was significantly increased in B cells (p = 0.0006131) and T cells (p = 0.00418) when comparing TL and ADMs. We also identified significant differences in IL-12 production by B cells (p = 0.0166) and T cells (p = 0.003636) when comparing TL and ADMs. CONCLUSIONS: Despite the assumed lack of an immunological response to ADMs, in our experimental study, human immune cells reacted with significantly different cytokine profiles. These findings may have implications for the potential activation or suppression of effector cells in cancerpatients and could explain some of the post clinical post surgical signs of ADMS like skin rush and seroma.
Entities:
Keywords:
Acellular dermal matrices; Breast cancer; IL-12; IL-6; Interleukin-12; Interleukin-6