T-cell therapy and immune checkpoint inhibitors are promising treatments for various forms of cancer. However, the response to immunotherapy varies from patient to patient and is heavily dependent on the performance of T-cells, specialized immune cells that can kill tumors. Tumors can negatively impact the fitness of T-cells, making them less effective in clearing tumor cells.
The four PhD students and postdocs on this project discovered that certain genes, such as Dap5, Icam1 and Ctbp1, play a significant role in affecting the condition of T-cells. In particular, they observed that disabling each of these genes allowed T-cells to become fitter in different ways, enabling them to attack tumors more effectively. In this study, the investigators therefore investigated which genes impact on the fitness of T-cells. They carried out so-called genome-wide screens in which they inactivated each of our 25,000 genes, to determine their contribution to T cell expansion, survival and activity.
Group leader Daniel Peeper: "These findings open the door to possible new strategies for improving immunotherapy. They could be applied in T-cell therapy, but that still needs to be tested. By selectively interfering with genes such as Dap5, Icam1 and Ctbp1, the proliferation and activity of T-cells can be optimized, potentially leading to a more sustainable and effective immune response against tumors".