ArticleProceedings of the National Academy of Sciences of the United States of America2012
Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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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
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Single-cell meta-analysis of T cells reveals clonal dynamics of response to checkpoint immunotherapy.Cell genomics · 2025Pooled it
- Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer.Cancer discovery · 2024Trial
- Review
- The Role of AP-1 in Cancer: Regulation, Tumor Microenvironment and Therapeutic Targeting.Biomolecules · 2026Review
- Claudin18.2 and the PD-1/PD-L1 axis in gastric cancer: mechanistic insights and implications for combination immunotherapy.Journal of translational medicine · 2026Review
- Article
- Posttranscriptional regulation of PD-1 by PRMT5/WDR77 complex shapes T cell effector function and antitumor immunity.The Journal of clinical investigation · 2026Article
- Exercise-induced βBrain, behavior, and immunity · 2025Article
- Modulating the PD-1-FABP5 axis in ILC2s to regulate adipose tissue metabolism in obesity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Leveraging T cells for cancer immunotherapy.Immunity & inflammation · 2025Review
- The role of immune checkpoint molecules in cancers.Frontiers in immunology · 2025Review
- LTβR deficiency causes lymph node aplasia and impaired B cell differentiation.Science immunology · 2024Article
- TMED inhibition suppresses cell surface PD-1 expression and overcomes T cell dysfunction.Journal for immunotherapy of cancer · 2024Article
- MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB.Signal transduction and targeted therapy · 2024Article
- Alternative Strategies for Delivering Immunotherapeutics Targeting the PD-1/PD-L1 Immune Checkpoint in Cancer.Pharmaceutics · 2024Review
- Article
- Exploring the Role of PD-1 in the Autoimmune Response: Insights into Its Implication in Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy.Cancers · 2024Review
- Article
- Hyperthermia in Combination with Emerging Targeted and Immunotherapies as a New Approach in Cancer Treatment.Cancers · 2024Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cells play a critical role in tumor immunosurveillance by eliminating newly transformed somatic cells. However, tumor cell variants can escape from immunological control after immunoediting, leading to tumor progression. Whether and how T cells respond to tumor growth remain unclear. Here, we found that tumor-infiltrating T cells exhibited persistently up-regulated expression of the activator protein 1 (AP-1) subunit c-Fos during tumor progression. The ectopic expression of c-Fos in T cells exacerbated tumor growth, whereas the T-cell-specific deletion of c-Fos reduced tumor malignancy. This unexpected immunosuppressive effect of c-Fos was mediated through the induced expression of immune inhibitory receptor programmed death 1 (PD-1) via the direct binding of c-Fos to the AP-1-binding site in the Pdcd1 (gene encoding PD-1) promoter. A knock-in mutation of this binding site abrogated PD-1 induction, augmented antitumor T-cell function and repressed tumor growth. Taken together, these findings indicate that T-cell c-Fos subsequently induces PD-1 expression in response to tumor progression and that disrupting such induction is essential for repression of tumor growth.
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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.