How T cells talk to the neighborhood: the spatiotemporal dynamics of T cell-derived cytokines in cancer

Abstract

To communicate with one another, cells in the body release signaling molecules called cytokines. The effects of these cytokines have been demonstrated to be extremely important for a successful immune response, but surprisingly little is known about how cytokines act in space and time. In this thesis, I describe the development of a set of new techniques that allow the efficient identification of cells that have encountered cytokine signals. Subsequently, I investigate the spreading of cytokines such as IFNγ and TNFα in in vivo cancer models and describe how activated cytotoxic T cells, which form a key compartment of our immune system, can profoundly modify the tumor microenvironment by the generation of widespread cytokine gradients.