ArticleThe Journal of experimental medicine2015
VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 6 registered trials, which are not on this map. Cited by 712 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase I/II Study of Pembrolizumab and Cabozantinib in Patients With Metastatic Renal Cell Carcinoma
Organ-specific Responses to Atezolizumab Plus Bevacizumab in Patients With Advanced Hepatocellular Carcinoma
Phase II Trial of Regorafenib in Patients With Unresectable Hepatocellular Carcinoma After Progression on First Line Atezolizumab Plus Bevacizumab (REGONEXT Trial)
A Single-arm Study of Toripalimab in Adjuvant Therapy After Resection of High-risk Renal Cancer
Ivonescimab Combined With Chemotherapy for EGFR Mutant NSCLC With Leptomeningeal Metastasis After EGFR TKIs Resistance: A Multicenter Observational Study.
Ivonescimab Combined With Polymeric Micelles Paclitaxel(Pm-Pac) and Platinum (Cisplatin/Carboplatin) as First-line Treatment for Patients With Advanced Squamous NSCLC: A Multicenter, Open-label, Single-arm Clinical Study.
Who cites it
712 citing papers in PubMed, 4 syntheses or guidelines pooled it, 1,129 citations in OpenAlex.
- Antibody-based regimens targeting PD-1/PD-L1 and VEGF/VEGFR in advanced or metastatic NSCLC: a meta-analysis of RCTs.Frontiers in immunology · 2026Pooled it
- Intracavitary perfusion with bevacizumab plus cisplatin versus cisplatin alone for malignant pleural effusion in lung cancer patients: a meta-analysis of randomized controlled trials.World journal of surgical oncology · 2025Pooled it
- VEGF-A in COVID-19: a systematic review and meta-analytical approach to its prognostic value.Clinical and experimental medicine · 2025Pooled it
- Hepatotoxicity of ICI monotherapy or combination therapy in HCC: A systematic review and meta-analysis.PloS one · 2025Pooled it
- Simlukafusp alfa (FAP-IL2v) plus atezolizumab with or without bevacizumab in unresectable, metastatic renal cell carcinoma: a randomized, open-label phase Ib study.Journal for immunotherapy of cancer · 2026Trial
- Distinct Spatially Resolved Tumor Microenvironment Trajectories Define Benefit from Ramucirumab plus Pembrolizumab in Refractory PD-L1+ Gastric Cancer.Cancer immunology research · 2026Trial
- Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial.Nature medicine · 2025Trial
- Serum VEGF-A as a biomarker for the addition of bevacizumab to chemo-immunotherapy in metastatic NSCLC.Nature communications · 2025Trial
- Anti-PD1 based precision induction therapy in unresectable stage III non-small cell lung cancer: a phase II umbrella clinical trial.Nature communications · 2025Trial
- A Phase II Open-Label, Randomized Clinical Trial of Atezolizumab with or without Human Recombinant IL-7 (CYT107) in Advanced Urothelial Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial.Nature communications · 2024Trial
- Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 Study.Lancet (London, England) · 2024Trial
- Surufatinib plus toripalimab combined with etoposide and cisplatin as first-line treatment in advanced small-cell lung cancer patients: a phase Ib/II trial.Signal transduction and targeted therapy · 2024Trial
- Identification of microenvironment features associated with primary resistance to anti-PD-1/PD-L1 + antiangiogenesis in gastric cancer through spatial transcriptomics and plasma proteomics.Molecular cancer · 2024Trial
- A Phase II Study of Potentiation of Pembrolizumab with Binimetinib and Bevacizumab in Refractory Microsatellite-Stable Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Immunomic longitudinal profiling of the NeoPembrOv trial identifies drivers of immunoresistance in high-grade ovarian carcinoma.Nature communications · 2024Trial
- Ramucirumab in combination with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma: a single-centre, phase 1/2 trial.The Lancet. Oncology · 2024Trial
- Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial.Nature medicine · 2024Trial
- Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Neoadjuvant camrelizumab and apatinib combined with chemotherapy versus chemotherapy alone for locally advanced gastric cancer: a multicenter randomized phase 2 trial.Nature communications · 2024Trial
652 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
18 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune escape is a prerequisite for tumor development. To avoid the immune system, tumors develop different mechanisms, including T cell exhaustion, which is characterized by expression of immune inhibitory receptors, such as PD-1, CTLA-4, Tim-3, and a progressive loss of function. The recent development of therapies targeting PD-1 and CTLA-4 have raised great interest since they induced long-lasting objective responses in patients suffering from advanced metastatic tumors. However, the regulation of PD-1 expression, and thereby of exhaustion, is unclear. VEGF-A, a proangiogenic molecule produced by the tumors, plays a key role in the development of an immunosuppressive microenvironment. We report in the present work that VEGF-A produced in the tumor microenvironment enhances expression of PD-1 and other inhibitory checkpoints involved in CD8(+) T cell exhaustion, which could be reverted by anti-angiogenic agents targeting VEGF-A-VEGFR. In view of these results, association of anti-angiogenic molecules with immunomodulators of inhibitory checkpoints may be of particular interest in VEGF-A-producing tumors.
Indexed as
Identifiers
What OpenQuestion holds
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.