Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
- Candidate categories
- Meta-epidemiology (narrow), Research integrity, Insufficient payload (model declined to judge)
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: Not applicableConsensus signal: Not applicable
- Genre
- Candidate signal: CommentaryConsensus signal: none
- Teacher disagreement score
- 0.390
- Threshold uncertainty score
- 1.000
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
- Teacher spread
- 0.241 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
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. SIGNIFICANCE: 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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
The record
- Venue
- Cancer Discovery
- Topic
- Telomeres, Telomerase, and Senescence
- Field
- Medicine
- Canadian institutions
- Université de MontréalCentre Hospitalier Universitaire Sainte-Justine
- Funders
- Departament d'Empresa i Coneixement, Generalitat de CatalunyaInstituto de Salud Carlos IIINatural Sciences and Engineering Research Council of CanadaFondation Charles-BruneauCentre de recherche du CHU Sainte-JustineFonds de Recherche du Québec - SantéHarald och Greta Jeanssons StiftelseBanco Bilbao Vizcaya ArgentariaVetenskapsrådetFundación Científica Asociación Española Contra el CáncerMinisterio de Ciencia e InnovaciónGeneralitat de CatalunyaCancerfondenAgència de Gestió d'Ajuts Universitaris i de RecercaCanadian Institutes of Health ResearchFundación Bancaria Caixa d'Estalvis i Pensions de BarcelonaFundación BBVAKarolinska InstitutetLoo och Hans Ostermans Stiftelse för Medicinsk ForskningInstitute for Research in BiomedicineInstitució Catalana de Recerca i Estudis AvançatsCanada Foundation for Innovation
- Keywords
- Immune systemSenescenceCD8Cytotoxic T cellBiologyAntigen presentationAcquired immune systemCancer cellMHC class ICell biologyAntigenContext (archaeology)Cross-presentationImmunogenic cell deathImmunologyT cellCancerImmunotherapyIn vitro
- Has abstract in OpenAlex
- yes