Zuazo Ibarra, MirenGato Cañas, MaríaLlorente, NoeliaIbañez Vea, MaríaArasanz Esteban, HugoKochan, GrazynaEscors Murugarren, David2022-08-082022-08-082017Zuazo, M.; Gato-Cañas, M.; Llorente, N.; Ibañez-Vea, M.; Arasanz, H.; Kochan, G.; Escors, D.. (2017). Molecular mechanisms of programmed cell death-1 dependent T cell suppression: relevance for immunotherapy. Annals of Translational Medicine. 5,19, pp. 385-391 .2305-583910.21037/atm.2017.06.11https://academica-e.unavarra.es/handle/2454/43729Programmed 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.application/pdfengCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 InternationalCancerImmune checkpoint inhibitorsImmunotherapyinfo:eu-repo/semantics/article2022-08-08info:eu-repo/semantics/openAccess