Funding
Generalitat de Catalunya (Government of Catalonia)
Fundación Científica Asociación Española Contra el Cáncer (AECC)
Fonds de Recherche du Québec - Santé (FRQS)
Cole Foundation (CF)
Centre de recherche du CHU Sainte-Justine (CHU Sainte-Justine Research Center)
Fondation Charles-Bruneau (Charles Bruneau Foundation)
Canada Foundation for Innovation (CFI)
Natural Sciences and Engineering Research Council of Canada (NSERC)
Canadian Institutes of Health Research (IRSC)
Karolinska Institutet (KI)
Vetenskapsrådet (VR)
Harald och Greta Jeanssons Stiftelse (Harald and Greta Jeansson Foundation)
Loo och Hans Ostermans Stiftelse för Medicinsk Forskning (Loo and Hans Osterman Foundation for Medical Research)
Cancerfonden (Swedish Cancer Society)
Institute for Research in Biomedicine (IRB Barcelona)
"la Caixa" Foundation ("la Caixa")
Ministerio de Ciencia e Innovación (MICINN)
European Research Council (ERC)
Institució Catalana de Recerca i Estudis Avançats (ICREA)
Departament d'Empresa i Coneixement, Generalitat de Catalunya (Ministry of Business and Knowledge, Government of Catalonia)
Instituto de Salud Carlos III (ISCIII)
Fundación BBVA (FBBVA)
ARTICLE ABSTRACT
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 (DC) and antigen-specific CD8 T cells. This includes the release of alarmins, activation of IFN signaling, enhanced MHC class I machinery, and presentation of senescence-associated self-peptides that can activate CD8 T cells. In the context of cancer, immunization with senescent cancer cells elicits strong antitumor 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 antitumor immune responses.
Our study shows that senescent cells are endowed with a high immunogenic potential—superior to the gold standard of immunogenic cell death. We harness these properties of senescent cells to trigger efficient and protective CD8-dependent antitumor immune responses.See related article by Chen et al., p. 432.This article is highlighted in the In This Issue feature, p. 247
