ArticleCancer research2023
Angiopoietin-2-Dependent Spatial Vascular Destabilization Promotes T-cell Exclusion and Limits Immunotherapy in Melanoma.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 39 citations in OpenAlex.
- Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial.Nature medicine · 2023Trial
- Spatial polarization of endothelial ICAM-1 governs T-cell exclusion in melanoma.EMBO molecular medicine · 2026Article
- CD8⁺ T Cell infiltration and spatial organization in cancer: mechanisms, barriers, and therapeutic strategies.Molecular biomedicine · 2026Review
- Leptomeningeal Collaterals Constitute an Immune-Responsive Vascular Niche in Ischemic Stroke.Stroke · 2026Article
- Myeloid-derived suppressor cells in cancer: biology, regulatory networks and theranostic prospects.Signal transduction and targeted therapy · 2026Review
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- USP21 drives immune evasion in colorectal cancer via deubiquitination and stabilization of β-catenin.Cellular & molecular immunology · 2026Article
- A Targetable Developmental Program Coregulates Angiogenesis and Immune Evasion in Melanoma.Cancer discovery · 2026Article
- The research progress of gastric cancer vaccines: a narrative review.Translational cancer research · 2026Review
- A novel prognostic model based on MVIRGs identifies ANGPT2 as a key target driving the malignant progression of HCC.Biological procedures online · 2026Article
- Review
- Pancreatic Lymphatics in Health and Disease: Evolution, Embryology, and Neural Control.Lymphatics · 2026Article
- Angiopoietin-2 aggravates Alzheimer's disease by promoting blood-brain barrier dysfunction and neuroinflammation.Cell reports · 2026Article
- Tumor immune-vascular crosstalk: synergy and translation of immune checkpoint inhibitors and anti-angiogenic agents in melanoma.Frontiers in immunology · 2026Review
- MAPK signaling and angiopoietin-2 contribute to endothelial permeability in capillary malformations.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.Biomarker research · 2025Review
- Tumour-associated vasculature in T cell homing and immunity: opportunities for cancer therapy.Nature reviews. Immunology · 2025Review
- Dual targeting of CDK4/6 and CDK7 augments tumor response and antitumor immunity in breast cancer models.The Journal of clinical investigation · 2025Article
- Integrated pan-cancer and melanoma-specific analysis of angiopoietin-2: prognostic value, immune microenvironment modulation, and ceRNA network regulation.Discover oncology · 2025Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
T-cell position in the tumor microenvironment determines the probability of target encounter and tumor killing. CD8+ T-cell exclusion from the tumor parenchyma is associated with poor response to immunotherapy, and yet the biology that underpins this distinct pattern remains unclear. Here we show that the vascular destabilizing factor angiopoietin-2 (ANGPT2) causes compromised vascular integrity in the tumor periphery, leading to impaired T-cell infiltration to the tumor core. The spatial regulation of ANGPT2 in whole tumor cross-sections was analyzed in conjunction with T-cell distribution, vascular integrity, and response to immunotherapy in syngeneic murine melanoma models. T-cell exclusion was associated with ANGPT2 upregulation and elevated vascular leakage at the periphery of human and murine melanomas. Both pharmacologic and genetic blockade of ANGPT2 promoted CD8+ T-cell infiltration into the tumor core, exerting antitumor effects. Importantly, the reversal of T-cell exclusion following ANGPT2 blockade not only enhanced response to anti-PD-1 immune checkpoint blockade therapy in immunogenic, therapy-responsive mouse melanomas, but it also rendered nonresponsive tumors susceptible to immunotherapy. Therapeutic response after ANGPT2 blockade, driven by improved CD8+ T-cell infiltration to the tumor core, coincided with spatial TIE2 signaling activation and increased vascular integrity at the tumor periphery where endothelial expression of adhesion molecules was reduced. These data highlight ANGPT2/TIE2 signaling as a key mediator of T-cell exclusion and a promising target to potentiate immune checkpoint blockade efficacy in melanoma. SIGNIFICANCE: ANGPT2 limits the efficacy of immunotherapy by inducing vascular destabilization at the tumor periphery to promote T-cell exclusion.
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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.