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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Detalles 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/192884
Acceso en línea:https://hdl.handle.net/2445/192884
Access Level:acceso abierto
Palabra clave:Cèl·lules canceroses
Immunitat cel·lular
Cancer cells
Cellular immunity
Descripción
Sumario: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.

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