ArticleNature2013
T-helper-1-cell cytokines drive cancer into senescence.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 435 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
435 citing papers in PubMed, 1 synthesis or guideline pooled it, 711 citations in OpenAlex.
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- Immune surveillance and immune evasion of senescent cells.Nature reviews. Immunology · 2026Review
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
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- Prognostic relevance of specific TIL (CD4+, CD8+, and FOXP3 + T-cell infiltrates) in triple-negative breast cancer: short- and long-term outcomes.Breast cancer (Tokyo, Japan) · 2026Article
- Cellular senescence in lung cancer immune microenvironment and senotherapeutic opportunities.iScience · 2026Review
- CD4Cancer biology & medicine · 2026Review
- Mutant KRAS vaccine with dual checkpoint blockade in resected pancreatic cancer: a phase I trial.Nature communications · 2026Article
- Harnessing Inflammatory Monocytes to Overcome Resistance to Anti-PD-1 Immunotherapy.bioRxiv : the preprint server for biology · 2026Article
- Filamin a binds deleted in liver cancer 1 (DLC1) to promote its tumor suppressor activity and inhibit the SRF coactivator MRTF-A.Neoplasia (New York, N.Y.) · 2026Article
- Recombinant human adenovirus type 5 synergizes with anti-PD-L1 antibody to promote anti-hepatocellular carcinoma effects through multilevel remodeling of the immune microenvironment.Frontiers in immunology · 2026Article
375 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer control by adaptive immunity involves a number of defined death and clearance mechanisms. However, efficient inhibition of exponential cancer growth by T cells and interferon-γ (IFN-γ) requires additional undefined mechanisms that arrest cancer cell proliferation. Here we show that the combined action of the T-helper-1-cell cytokines IFN-γ and tumour necrosis factor (TNF) directly induces permanent growth arrest in cancers. To safely separate senescence induced by tumour immunity from oncogene-induced senescence, we used a mouse model in which the Simian virus 40 large T antigen (Tag) expressed under the control of the rat insulin promoter creates tumours by attenuating p53- and Rb-mediated cell cycle control. When combined, IFN-γ and TNF drive Tag-expressing cancers into senescence by inducing permanent growth arrest in G1/G0, activation of p16INK4a (also known as CDKN2A), and downstream Rb hypophosphorylation at serine 795. This cytokine-induced senescence strictly requires STAT1 and TNFR1 (also known as TNFRSF1A) signalling in addition to p16INK4a. In vivo, Tag-specific T-helper 1 cells permanently arrest Tag-expressing cancers by inducing IFN-γ- and TNFR1-dependent senescence. Conversely, Tnfr1(-/-)Tag-expressing cancers resist cytokine-induced senescence and grow aggressively, even in TNFR1-expressing hosts. Finally, as IFN-γ and TNF induce senescence in numerous murine and human cancers, this may be a general mechanism for arresting cancer progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.