TY - JOUR AU - Zuazo, Miren AU - Gato-Cañas, Maria AU - Llorente, Noelia AU - Ibañez-Vea, María AU - Arasanz, Hugo AU - Kochan, Grazyna AU - Escors, David PY - 2017 TI - Molecular mechanisms of programmed cell death-1 dependent T cell suppression: relevance for immunotherapy JF - Annals of Translational Medicine; Vol 5, No 19 (October 28, 2017): Annals of Translational Medicine (Focus on “II Meeting on Traslational Research on Melanoma by the Spanish Melanoma Group (GEM)”) Y2 - 2017 KW - N2 - Programmed cell death-1 (PD1) has become a significant target for cancer immunotherapy. PD1 and its receptor programmed cell death 1 ligand 1 (PDL1) are key regulatory physiological immune checkpoints that maintain self-tolerance in the organism by regulating the degree of activation of T and B cells amongst other immune cell types. However, cancer cells take advantage of these immunosuppressive regulatory mechanisms to escape T and B cell-mediated immunity. PD1 engagement on T cells by PDL1 on the surface of cancer cells dramatically interferes with T cell activation and the acquisition of effector capacities. Interestingly, PD1-targeted therapies have demonstrated to be highly effective in rescuing T cell anti-tumor effector functions. Amongst these the use of anti-PD1/PDL1 monoclonal antibodies are particularly efficacious in human therapies. Furthermore, clinical findings with PD1/PDL1 blockers over several cancer types demonstrate clinical benefit. Despite the successful results, the molecular mechanisms by which PD1-targeted therapies rescue T cell functions still remain elusive. Therefore, it is a key issue to uncover the molecular pathways by which these therapies exert its function in T cells. A profound knowledge of PDL1/PD1 mechanisms will surely uncover a new array of targets susceptible of therapeutic intervention. Here, we provide an overview of the molecular events underlying PD1-dependent T cell suppression in cancer. UR - https://atm.amegroups.org/article/view/15376