ArticleCancer research2013
Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 415 papers, 3 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
415 citing papers in PubMed, 3 syntheses or guidelines pooled it, 736 citations in OpenAlex.
- Efficacy and safety of anti-PD-1/PD-L1-based dual immunotherapies versus PD-1/PD-L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta-analysis.Cancer immunology, immunotherapy : CII · 2024Pooled it
- Systematic review of combinations of targeted or immunotherapy in advanced solid tumors.Journal for immunotherapy of cancer · 2021Pooled it
- Comparative Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Advanced Cancer: A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2020Pooled it
- Maveropepimut-S, pembrolizumab and low dose cyclophosphamide in metastatic ovarian cancer: phase 1/2 PESCO trial.Nature communications · 2026Trial
- Neoadjuvant immune checkpoint blockade before chemoradiation for cervical squamous carcinoma (GINECO window-of-opportunity COLIBRI study): a phase II trial.Nature communications · 2026Trial
- Depletion of Effector Regulatory T Cells Associates with Major Response to Induction Dual Immune Checkpoint Blockade.Cancer discovery · 2025Trial
- Nivolumab plus low-dose ipilimumab in hypermutated HER2-negative metastatic breast cancer: a phase II trial (NIMBUS).Nature communications · 2025Trial
- Randomized Phase II Trial of Nivolumab Versus Nivolumab and Ipilimumab for Recurrent or Persistent Ovarian Cancer: An NRG Oncology Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Therapeutic cancer vaccines: development, challenges, and future perspectives.Acta pharmacologica Sinica · 2026Review
- Overall survival of immunotherapy versus standard of care in chemorefractory microsatellite stable metastatic colorectal cancer: a propensity score matched analysis of 708 patients.Journal for immunotherapy of cancer · 2026Article
- Efficacy and Safety of Cadonilimab in Digestive System Neoplasms: A Systematic Review and Single-Arm Meta-Analysis.Pharmaceuticals (Basel, Switzerland) · 2026Review
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- Review
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- CTLA-4 Blockade Combined with PD-1/PD-L1 Inhibition Enhances Cytokine Production and T-Cell Activation in Ex Vivo Ovarian Cancer Cultures.International journal of molecular sciences · 2026Article
- Additive anti-tumor and immunomodulatory effects of Sporoderm-removed Ganoderma lucidum spore powder and anti-PD-L1 antibody in lung cancer mice.Discover oncology · 2026Article
- MAP4K2 suppresses antitumor immunity in a pancreatic cancer model by promoting Treg differentiation.The Journal of clinical investigation · 2026Article
- Advances in immunotherapy for colorectal cancer: overcoming resistance in mismatch repair-proficient tumors.Cancer cell international · 2026Review
- Stoking an anti-liver cancer immune response with cryoablation plus an intratumoral TLR9 agonist and dual checkpoint inhibitors.Cancer immunology, immunotherapy : CII · 2026Article
- The impact of chronic comorbidities on cancer immunoediting: challenges and opportunities for immunotherapies.Frontiers in immunology · 2026Review
355 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Tumor progression is facilitated by regulatory T cells (Treg) and restricted by effector T cells. In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression.
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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.