ArticleNature cancer2021
Targeting PAK4 to reprogram the vascular microenvironment and improve CAR-T immunotherapy for glioblastoma.
Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- T cell immunity in glioma and potential implications for immunotherapy: A systematic review.Neuro-oncology · 2026Pooled it
- Biomimetic membrane-coated metal nanoplatforms for enhanced BBB penetration and targeted glioblastoma therapy.International journal of pharmaceutics: X · 2026Review
- Targeting claudins in cancer.Nature reviews. Drug discovery · 2026Review
- Design optimization of antibody-ligand motifs to enhance CAR-T redirection activity against solid tumors.Cell reports. Medicine · 2026Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- An epigenetic switch in vascular phenotype augments anti-tumor immunity.Angiogenesis · 2026Article
- The interplay between p21-activated kinases and tumour-infiltrating dendritic cells and T cells and its implication in pancreatic cancer immunotherapy.Cell communication and signaling : CCS · 2026Review
- Investigating PAK inhibition in combination with PD-1 blockade to enhance cytotoxic CD8+ T cell-mediated killing and suppress invasion of ovarian cancer cells.British journal of cancer · 2026Article
- Claudin proteins as emerging therapeutic targets for solid tumours.Nature reviews. Cancer · 2026Review
- Article
- Dissecting the aberrant vasculature of glioblastoma: mechanisms and therapeutic targets.Cancer metastasis reviews · 2026Review
- Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy.Acta pharmaceutica Sinica. B · 2026Review
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Review
- Article
- SLC7A5 promotes vascular remodeling in the rat carotid artery following balloon injury through PI3K/Akt signaling pathway.Frontiers in pharmacology · 2026Article
- Globulol fromFrontiers in pharmacology · 2026Article
- Article
- Ionizing radiation enhances CAR T-cell infiltration and efficacy in solid tumors.Frontiers in immunology · 2026Article
- CAR T Cell Therapy in Lung Cancer: Overcoming Tumor Microenvironment-Mediated Barriers.International journal of biological sciences · 2026Review
29 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
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Malignant solid tumors are characterized by aberrant vascularity that fuels the formation of an immune-hostile microenvironment and induces resistance to immunotherapy. Vascular abnormalities may be driven by pro-angiogenic pathway activation and genetic reprogramming in tumor endothelial cells (ECs). Here, our kinome-wide screening of mesenchymal-like transcriptional activation in human glioblastoma (GBM)-derived ECs identifies p21-activated kinase 4 (PAK4) as a selective regulator of genetic reprogramming and aberrant vascularization. PAK4 knockout induces adhesion protein re-expression in ECs, reduces vascular abnormalities, improves T cell infiltration and inhibits GBM growth in mice. Moreover, PAK4 inhibition normalizes the tumor vascular microenvironment and sensitizes GBM to chimeric antigen receptor-T cell immunotherapy. Finally, we reveal a MEF2D/ZEB1- and SLUG-mediated mechanism by which PAK4 reprograms the EC transcriptome and downregulates claudin-14 and VCAM-1 expression, enhancing vessel permeability and reducing T cell adhesion to the endothelium. Thus, targeting PAK4-mediated EC plasticity may offer a unique opportunity to recondition the vascular microenvironment and strengthen cancer immunotherapy.
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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.