Cellular senescence is immunogenic and promotes anti-tumor immunity

Cellular senescence is a stress response that activates innate immune cells, but little is known about its interplay with the adaptive immune system. Here, we show that senescent cells combine several features that render them highly efficient in activating dendritic cells (DCs) and antigen-specific...

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Detalhes bibliográficos
Autores: Marin, Ines, Boix, Olga, Garcia Garijo, Andrea, Sirois, Isabelle, Caballe, Adrià, Zarzuela, Eduardo, Ruano, Irene, Stephan-Otto Attolini, Camille, Prats, Neus, López Domínguez, José A., Kovatchev, Marta, Garralda, Elena, Muñoz, Javier, Caron, Etinne, Abad, María, Gros, Alena, Pietrocola, Federico, Serrano Marugán, Manuel
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/192884
Acesso em linha:https://hdl.handle.net/2445/192884
Access Level:acceso abierto
Palavra-chave:Cèl·lules canceroses
Immunitat cel·lular
Cancer cells
Cellular immunity
Descrição
Resumo:Cellular senescence is a stress response that activates innate immune cells, but little is known about its interplay with the adaptive immune system. Here, we show that senescent cells combine several features that render them highly efficient in activating dendritic cells (DCs) and antigen-specific CD8 T cells. This includes the release of alarmins, activation of interferon signaling, enhanced MHC class I machinery, and presentation of senescence-specific self-peptides that can activate CD8 T cells. In the context of cancer, immunization with senescent cancer cells elicits strong anti-tumor protection mediated by DCs and CD8 T cells. Interestingly, this protection is superior to immunization with cancer cells undergoing immunogenic cell death. Finally, the induction of senescence in human primary cancer cells also augments their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. Our study indicates that senescent cancer cells can be exploited to develop efficient and protective CD8-dependent anti-tumor immune responses.