The Kabelitz group investigates the modulation of activation and effector activity of human γδ T cells by vitamins (e.g., vitamin C), selected cytokines, and ligands for the Notch receptor. Our goal is to improve and optimize the effector function of γδ T cells for future clinical application in cancer immunotherapy.
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In contrast to conventional CD4 and CD8 T cells, γδ T cells do not recognize peptides but rather intermediates of the cholesterol metabolism (pyrophosphates) which are overproduced by tumor cells in comparison to healthy cells. As a consequence, γδ T cells can recognize and kill tumor cells independently of HLA molecules, which makes γδ T cells attractive effector cells for immunotherapy (1,2). Importantly, it has been already shown that γδ T cells can be safely isolated from allogeneic healthy donors for subsequent adoptive transfer into cancer patients (3). On the other hand, it is obvious that the effector function of γδ T cells requires optimization in order to improve the clinical efficacy of γδ T-cell based cancer immunotherapy (1,4).
Our group investigates the modulation of activation and effector activity of human γδ T cells by vitamins including vitamin C (5,6,7), and by ligands for the Notch receptor and cGAS/STING (8,9). We have developed short-term activation assays to investigate the γδ T-cell responsiveness to different stimuli (10), and we also study the functional capacity of γδ T cells in tuberculosis and acute influenza infections.