Molecular mechanisms of programmed cell death-1 dependent T cell suppression: relevance for immunotherapy
Fecha
2017Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Impacto
|
10.21037/atm.2017.06.11
Resumen
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 ...
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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. [--]
Materias
Cancer,
Immune checkpoint inhibitors,
Immunotherapy
Editor
AME Publishing
Publicado en
Annals of Translational Medicine, 2017, 5 (19), pp. 385-391
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
The authors gratefully acknowledge the Gobierno de Navarra, the ‘Precipita’ crowdfunding project grant from Fundación Española para la Ciencia y la Tecnología (FECYT), ‘Sandra Ibarra’ Foundation, the ‘Navarrese Association against Breast Cancer’ (SARAY), ‘Caixa Foundation’ and ISCIII (FIS. PI14/00579 project grant) for their financial support. Funding: M Gato-Cañas is funded by a Government of Navarre PhD fellowship (BMED 033-2014); M Zuazo is funded by PhD studentship from the Universidad Pública de Navarra; M Ibañez-Vea is funded by a Sara Borrel post-doctoral fellowship. D Escors is funded by a ‘Miguel Servet’ Fellowship (CP12/03114) from the Instituto de Salud Carlos III (ISCIII), Spain. G Kochan is funded by a ‘Proyecto Tractor ProCel’ from the Government of Navarre