ArticleJCI insight2018
Integrin αvβ8-expressing tumor cells evade host immunity by regulating TGF-β activation in immune cells.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 111 citations in OpenAlex.
- Cold and hot tumors: immunological determinants, cancer-immunity cycle dysregulation, and nanotechnology-driven therapeutic approaches.Molecular biomedicine · 2026Review
- Multi-omic Profiling of Recurrence Risk Across Breast Cancer Subtypes.medRxiv : the preprint server for health sciences · 2026Article
- Proteogenomic decoding of chemotherapy resistance in patients with triple-negative breast cancer.Genome biology · 2026Article
- ITGB1 Regulates Triple-Negative Breast Cancer Development by Modulating the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Selective blockade of latent TGF-β1 activation suppresses tissue fibrosis with good safety.Communications medicine · 2026Article
- Article
- Gut dysbiosis from high-salt diet promotes glioma via propionate-mediated TGF-β activation.The Journal of experimental medicine · 2025Article
- Tumor Microenvironment On-A-Chip and Single-Cell Analysis Reveal Synergistic Stromal-Immune Crosstalk on Breast Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Blockade of αvβ6 and αvβ8 integrins with a chromogranin A-derived peptide inhibits TGFβ activation in tumors and suppresses tumor growth.Journal of experimental & clinical cancer research : CR · 2025Article
- Substrate interactions guide cyclase engineering and lasso peptide diversification.Nature chemical biology · 2025Article
- Specifically blocking αvβ8-mediated TGF-β signaling to reverse immunosuppression by modulating macrophage polarization.Journal of experimental & clinical cancer research : CR · 2025Article
- Histidine-rich glycoprotein inhibits TNF-α-induced tube formation in human vascular endothelial cells.Frontiers in pharmacology · 2025Article
- ITGA4 as a potential prognostic and immunotherapeutic biomarker in human cancer and its clinical significance in gastric cancer: an integrated analysis and validation.Frontiers in oncology · 2025Article
- Senescence-associated secretory phenotype in lung cancer: remodeling the tumor microenvironment for metastasis and immune suppression.Frontiers in oncology · 2025Review
- The integrin adhesome and control of anti-tumour immunity.Biochemical Society transactions · 2024Review
- Exosomal integrins in tumor progression, treatment and clinical prediction (Review).International journal of oncology · 2024Review
- Article
- Integrating integrins with the hallmarks of cancer.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
TGF-β is a promising immunotherapeutic target. It is expressed ubiquitously in a latent form that must be activated to function. Determination of where and how latent TGF-β (L-TGF-β) is activated in the tumor microenvironment could facilitate cell- and mechanism-specific approaches to immunotherapeutically target TGF-β. Binding of L-TGF-β to integrin αvβ8 results in activation of TGF-β. We engineered and used αvβ8 antibodies optimized for blocking or detection, which - respectively - inhibit tumor growth in syngeneic tumor models or sensitively and specifically detect β8 in human tumors. Inhibition of αvβ8 potentiates cytotoxic T cell responses and recruitment of immune cells to tumor centers - effects that are independent of PD-1/PD-L1. β8 is expressed on the cell surface at high levels by tumor cells, not immune cells, while the reverse is true of L-TGF-β, suggesting that tumor cell αvβ8 serves as a platform for activating cell-surface L-TGF-β presented by immune cells. Transcriptome analysis of tumor-associated lymphoid cells reveals macrophages as a key cell type responsive to β8 inhibition with major increases in chemokine and tumor-eliminating genes. High β8 expression in tumor cells is seen in 20%-80% of various cancers, which rarely coincides with high PD-L1 expression. These data suggest tumor cell αvβ8 is a PD-1/PD-L1-independent immunotherapeutic target.
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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.