ArticleAngiogenesis2023
Proinflammatory activity of VEGF-targeted treatment through reversal of tumor endothelial cell anergy.
Article in Angiogenesis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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
36 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting the Barriers Driving Immune Exclusion.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Study on the Effect of Antibiotics on the Efficacy of PD-1 Inhibitors and Its Regulatory Mechanism via the Intestinal Bacterial Community.Biochemical genetics · 2026Article
- The vascular contribution to immunotherapy success.Angiogenesis · 2026Article
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- Charge-flip nanoparticles loaded with TAK1 inhibitors inhibit retinal neovascularization.Journal of nanobiotechnology · 2026Article
- Anti-angiogenic therapies in cancer: from endogenous inhibitors to bispecific VEGF x PD-(L)1 antibodies.Frontiers in immunology · 2026Review
- LGMNFrontiers in immunology · 2026Article
- Serial assessment of inflammatory biomarkers as a prognostic factor for first-line treatment outcomes in patients with metastatic colorectal cancer: single-center retrospective study.Frontiers in oncology · 2026Article
- Multifunctional nanoplatforms for tumor microenvironment remodeling: Toward precision and intelligent cancer therapy.Materials today. Bio · 2025Review
- Neoadjuvant immunotherapy in squamous cell carcinoma of the head and neck: current evidence and future perspectives.Molecular cancer · 2025Review
- The Vulnerable Vascular Network: Endothelial Dysfunction as a Central Driver of Intestinal Inflammation-A Systematic Review.Biomedicines · 2025Review
- Vaccination Against Extracellular Vimentin Plus Doxorubicin for Canine Hemangiosarcoma.International journal of molecular sciences · 2025Article
- Zinc-doped curcumin carbon dots promote infected wound healing with photodynamic via the VEGF signaling pathway.Journal of nanobiotechnology · 2025Article
- Angiogenesis and targeted therapy in the tumour microenvironment: From basic to clinical practice.Clinical and translational medicine · 2025Review
- Embryonic reprogramming of the tumor vasculature reveals targets for cancer therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Bioinformatics analysis and experimental validation ofBiomolecules & biomedicine · 2025Article
- Engineering Nanoparticles to Modulate Extracellular Matrix and Immune Components of the Tumor Microenvironment in Cancer Immunotherapy.Biomaterials research · 2025Review
- Infiltration characteristics and regulatory mechanisms of CD8Frontiers in immunology · 2025Review
- Recent progress on tyrosine kinase inhibitors resistance in renal cell carcinoma: another brick in the wall?Cancer drug resistance (Alhambra, Calif.) · 2025Review
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 10 institutions in 4 countries.
Funding
Abstract
purposeOngoing angiogenesis renders the tumor endothelium unresponsive to inflammatory cytokines and interferes with adhesion of leukocytes, resulting in escape from immunity. This process is referred to as tumor endothelial cell anergy. We aimed to investigate whether anti-angiogenic agents can overcome endothelial cell anergy and provide pro-inflammatory conditions. EXPERIMENTAL
designTissues of renal cell carcinoma (RCC) patients treated with VEGF pathway-targeted drugs and control tissues were subject to RNAseq and immunohistochemical profiling of the leukocyte infiltrate. Analysis of adhesion molecule regulation in cultured endothelial cells, in a preclinical model and in human tissues was performed and correlated to leukocyte infiltration.
resultsIt is shown that treatment of RCC patients with the drugs sunitinib or bevacizumab overcomes tumor endothelial cell anergy. This treatment resulted in an augmented inflammatory state of the tumor, characterized by enhanced infiltration of all major leukocyte subsets, including T cells, regulatory T cells, macrophages of both M1- and M2-like phenotypes and activated dendritic cells. In vitro, exposure of angiogenic endothelial cells to anti-angiogenic drugs normalized ICAM-1 expression. In addition, a panel of tyrosine kinase inhibitors was shown to increase transendothelial migration of both non-adherent and monocytic leukocytes. In primary tumors of RCC patients, ICAM-1 expression was found to be significantly increased in both the sunitinib and bevacizumab-treated groups. Genomic analysis confirmed the correlation between increased immune cell infiltration and ICAM-1 expression upon VEGF-targeted treatment.
conclusionThe results support the emerging concept that anti-angiogenic therapy can boost immunity and show how immunotherapy approaches can benefit from combination with anti-angiogenic compounds.
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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 Socratic graph.