Cytotoxic T lymphocytes (CTL) are nature’s key weapon against intracellular infections and are therapeutically harnessed to defend us against cancer. We are interested in (costimulatory) membrane receptors, associated signal transduction pathways and gene expression programs that shape the CTL response. Herein, we focus on communication between T cells and dendritic cells (DCs). We examine transcriptional and epigenetic regulation that shapes effector and memory functions of T cells We are in particular breaking new ground in discovering how CD4+ helper T cells program CTL function. These insights can enable discovery of new targets for immune oncology drugs or new therapeutic vaccination approaches.
We also investigate costimulatory and coinhibitory receptor signaling in conventional versus regulatory CD4+ T cells that respectively promote or inhibit tumor immunity. We explore by transcriptomics, proteomics and metabolomics the molecular programs underlying responses of these T cell subsets. We do this work to enable selective drug targeting of each cellular subset. We work with chemists in the Institute for Chemical Immunology (ICI) Gravitation program for this purpose.
We are furthermore interested in the concept of immunogenic cell death and its role in eliciting systemic anti-tumor CTL responses that we explore in the context of radio- and chemotherapy.