T cell differentiation

CD8+ T cells are critical to fight microbial infections and to clear cancer cells. They block pathogen spreading and they clear infected cells and tumor cells from the body. A crucial feature of T cell effector function is the release of three important cytokines: Tumor Necrosis Factor alpha (TNF-α), Interferon gamma (IFN-γ) and Interleukin 2 (IL-2). Whereas their transcription regulation is well studied, transcript levels poorly predict actual cytokine production. For instance, chronic activation of T cells e.g. in the tumor environment blocks their capacity to produce cytokines, yet substantial levels of cytokine mRNA is detected in tumor-infiltrating T cells. We therefore investigate molecular mechanisms that define the levels of cytokine production in effector T cells and in exhausted T cells, with a focus on post-transcriptional regulation. We aim to manipulate these mechanisms to reprogram exhausted tumor-infiltrating T cells back into proficient effector T cells. My lab has two research lines that combine fundamental research questions with preclinical studies to explore the possibility to improve T cell effector function for human T cell therapy.