Elucidating the mechanism underlying the IFNγ-mediated sensitisation to TNF-induced cell death

In recent years, a significant focus of cancer research has been on understanding the interaction between cancer cells, the immune system and the tumor microenvironment. Cytotoxic immune cells, such as CD8+ T-cells and NK-cells, play a crucial role in eradicating cancer cells. An important killing mechanism used by these cells is the expression of death ligands like TNF, TRAIL, and FasL on their surface. Interestinglyin vitro treatment of cancer cells with IFNγ strongly sensitizes them to death ligand-mediated killing, yet the precise molecular mechanism behind this sensitization remains unknown.

The primary goal of my project is to unravel this mechanism as this may offer new pharmacological and therapeutic targets for two distinct disease types. Exploiting or replicating the observed IFNγ-mediated sensitization could significantly enhance the effectiveness of T- or NK-cell-based cancer immunotherapies. Conversely, blocking the IFNγ -mediated sensitization may be beneficial for the treatment of inflammatory cell death  driven autoimmune diseases where pro-inflammatory cytokines like IFNγ are highly abundant.

By investigating this mechanism, my project aims to contribute to advancements in both cancer immunotherapy and the management of inflammatory autoimmune diseases.

Walczak Lab (uni-koeln.de)