15th Day of Clinical Research 2016 - Posterpreise

Im Namen der Klinikleitung freuen wir uns sehr darüber und gratulieren ganz herzlich zu den gewonnenen Posterpreisen des 'Day of Clinical Research 2016'

Frau Natalia Arenas Ramirez für ihr Poster "Blocking of the epigenetic repressor Ezh2 controls tumor escape upon IL-2cx immunotherapy"

Frau Janine Woytschak für ihr Poster "Type II IL-4 receptor expression on neutrophils antagonizes their expansion and migration during infection and inflammation"


Natalia Venetz-Arenas.pngNatalia Arenas Ramirez, MSc
High dose human Interleukin-2 (hIL-2) has shown clinical response rates of 15-19 % in patients with metastatic cancer. However, its clinical application is limited by adverse effects such as vascular leak syndrome, stimulation of T regulatory (Treg) cells and a short half-life. In order to modulate hIL-2 activity, Natalia Arenas Ramirez and colleagues generated a unique anti-human IL-2 antibody: NARA1. By blocking the CD25 receptor binding site of the cytokine, hIL-2 complexed with NARA1 preferentially stimulates effector CD122high (CD8+ T and NK cells) over immunosuppressive Treg cells. Human IL-2/NARA1 complexes generate potent anti-tumor responses controlling metastasis development along with a prolonged half-life. As for many cancer therapies, despite initial control the tumor usually relapses. During this process, the levels of the epigenetic modifier Ezh2 increase leading to poorly immunogenic transformed cancer cells. This effect is reversed by blocking Ezh2 leading to a more potent and prolonged tumor control in combination with hIL-2/NARA1 therapy.

Janine Woytschak.png Janine Woytschak, PhD
Neutrophils are the first immune cells recruited to sites of inflammation and infection. However, patients with allergic disorders such as atopic dermatitis show a paucity of skin neutrophils and are prone to bacterial skin infections, suggesting that allergic ‘type-2’ inflammation might curtail neutrophil responses. Given that interleukin (IL)-4 is instrumental in initiating, polarizing and maintaining type-2 immunity, these findings beg the question whether IL-4 signals directly affect neutrophil expansion, migration or function. 
Janine Woytschak and colleagues show that the type-2 signature cytokine IL-4 hampers neutrophil expansion and migration by antagonizing G-CSF and chemokine receptor-mediated signals. Cutaneous bacterial infection in mice was exacerbated by IL-4 signaling and improved when IL-4 was blocked, with each outcome inversely correlating with neutrophil migration to skin. Likewise, systemic bacterial infection was worsened by heightened IL-4 activity, with IL-4 restricting G-CSF-induced neutrophil expansion in and migration from bone marrow to tissues by disrupting CXCR2–CXCR4 chemokine signaling in neutrophils. These effects were dependent on IL-4 acting through type II IL-4 receptors (consisting of IL-4Rα and IL-13Rα1) on neutrophils, inducing thereby p38 MAPK phosphorylation.