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Homeostatic PD-1 signaling restrains EOMES-dependent oligoclonal expansion of liver-resident CD8 T cells


Immune checkpoint blocade (ICB) therapy has revolutionised the treatment of certain cancers by enabling reactivation of our own lymphocytes to fight tumour cells. Unfortunately, these treatments can be associated with significant side-effects, as they also block important mechanisms that confer tolerance to our healthy cells. It is therefore important to understand the physiological role of these regulatory pathways in order to prevent the complications associated with immunotherapy. In a work published in Cell Reports, Marie Le Moine and colleagues from the teams of Stanislas Goriely, Fabienne Andris and David Vermeylen have highlighted the central role of the PD-1 pathway in keeping resident T lymphocytes at rest in the liver. Reactivation of these immune cells could therefore be the cause of the liver toxicities observed in some patients undergoing anti-PD-1/PDL-1 treatments. These results could lead to improvements in current ICB treatments by reducing their undesirable effects.

Original article : Marie Le Moine et al, Homeostatic PD-1 signaling restrains EOMES-dependent oligoclonal expansion of liver-resident CD8 T cells, Cell Reports 2023