NG Wirsdörfer –
Immunmodulation

Research focus

Radiation-induced immune changes in normal and tumor tissue

Radiotherapy is an integral part of standard treatment for various neoplasms. On the one hand, treatment is limited by intrinsic tumor resistance and by metabolic and microenvironment-induced adaptive resistance of the tumor. On the other hand, radiation-induced normal tissue toxicity and immune-related undesirable side effects limit the course of therapy, so that ultimately different treatment successes are achieved in the patients. These limitations restrict the therapeutic window, which leads to suboptimal local control, metastasis formation and a reduced quality of life.

The research work of the junior research group “Immunomodulation” aims to elucidate the interaction between the damage to the tumor or normal tissue as a result of radiation, the activation of the innate and adapted immune system, and the development of adverse side effects.

The focus of the junior research group is on the mechanisms underlying the radiation-induced toxicity of normal lung tissue. The aim is to define new therapeutic targets with different effects in tumor and normal tissue in order to develop effective treatments that protect normal tissue without compromising tumor control. In addition, the group pursues translational research approaches by investigating the risk of new combinatorial radiotherapies with a focus on immunotherapeutics.

This involves co-clinical irradiation systems, immunophenotyping using multicolor flow cytometry and advanced imaging techniques such as PET-CT, multiplex and lightsheet microscopy as well as cytokine profiling.

Previous research has revealed pathologic acute and chronic immune modulations associated with radiation-induced side effects in the lung, e.g. local immune activation and systemic accumulation of immunosuppressive CD4+ T cell populations and increased CD39/CD73 activity. Current projects of the research group focus on the development of novel therapeutic targets to reduce radiation-induced normal tissue toxicity in NSCLC and HNSCC and on deciphering the complex immune-related side effects that may occur in the course of novel therapeutic approaches with radio(chemo)therapy and immune checkpoint inhibition. The main long-term goals of the research group are therefore to define predictive biomarkers for the risk assessment and detection of radiation-induced acute and chronic tissue damage and ultimately to identify new therapeutic targets to overcome treatment limitations