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 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, 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
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