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T cell differentiation

Introduction

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 the transcriptional and post-transcriptional mechanisms that define the levels of cytokine production in effector T cells and in exhausted T cells. We aim to manipulate these mechanisms to reprogram exhausted tumor-infiltrating T cells back into proficient effector T cells. My lab has three 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.

Medical need:

Cancer

Funding:

  • Oncode Institute (national academic partnership in the field of cancer research)
  • ERC consolidator grant (European Research Council)
  • LSBR fellowship (Landsteiner Foundation for Blood Transfusion Research)
  • NWO-VIDI (Dutch Research Council)
  • PPOC (internal funding in competition)
  • KWF

 

Our research