Professor Henning Walczak

TUMOUR IMMUNOLOGY

In the Tumour Immunology Unit we aim to understand the mechanisms used by the immune system to specifically attack cancer cells and to uncover the mechanisms employed by tumours to counteract these. We want to use this information to devise new treatment strategies for cancer based on specifically killing tumour cells. This can be achieved in two ways; indirectly by stimulating cells of the immune system to specifically attack tumour cells or directly by employing the very molecules normally used by the immune system to kill tumour cells.

Both processes, stimulation of immune cells and specific killing of tumour cells, are mainly regulated and induced by two protein families, the proteins belonging to the tumour necrosis factor (TNF) superfamily of cytokines and their corresponding receptors. Therefore, research in the Tumour Immunology Unit focuses on the study of TNF and TNF receptor superfamily members.

Some of the members of the TNF family of cytokines induce programmed cell death by apoptosis. Apoptosis is a fundamental biological process. Under normal conditions there is a precisely regulated balance between cell death and cell proliferation. This balance ensures tissue homoeostasis. Malfunctioning of the cell suicide programme plays a critical role in development and persistence of a number of diseases including cancer and autoimmunity. We focus on using the TNF-related apoptosis-inducing ligand (TRAIL) in combination with other targeted or conventional cancer drugs to efficiently kill tumour cells. By identifying particular TRAIL-comprising drug combinations that are most suitable for individual cancer patients with a particular marker profile we aim to achieve in the future the personalised treatment of cancer with optimised efficacy.

Other TNF family members mediate immunity-inducing and/or inflammatory signalling which often counteracts the induction of apoptosis. Phosphorylation and different ubiquitination events, including the generation of linear ubiquitin chains, are central to these signal transduction processes. It is the aim of the Tumour Immunology Unit to decipher the exact mechanisms involved in these signalling processes. We are particularly interested in determining how linear ubiquitin chains enable inflammatory and immunity-inducing signalling events and how they cooperate with other types of ubiquitin chains to achieve this.