ArticleProceedings of the National Academy of Sciences of the United States of America2019
αvβ3-integrin regulates PD-L1 expression and is involved in cancer immune evasion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers.
What it found
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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
64 citing papers in PubMed, 81 citations in OpenAlex.
- Synergistic Regulation of Tumor Immunity by Integrins and Lectins: From Molecular Mechanisms to Dual-Targeted Therapy.International journal of molecular sciences · 2026Review
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Article
- Integrins as key regulators in tumor perineural invasion: mechanisms and clinical implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- ITGB1 Regulates Triple-Negative Breast Cancer Development by Modulating the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrin αvβ3-dependent pathogenic effect and therapeutic effects of DL-N2 combined with EGFR inhibitors in pancreatic adenocarcinoma.Journal of translational medicine · 2026Article
- Comparative safety analysis of enfortumab vedotin and pembrolizumab: monotherapy vs. combination therapy insights from FDA adverse event reporting system data.World journal of urology · 2026Article
- Immune regulatory mechanisms in the tumor microenvironment and their applications in cancer therapy: from basic research to clinical translation.Frontiers in immunology · 2026Review
- Cancer Immunotherapy via Disruption of Integrin αvβ3 and CD47 Costabilization on Cancer Cell Surface.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Membrane and soluble VTCN1 (B7H4) converge on Src signaling to mediate gemcitabine resistance in intrahepatic cholangiocarcinoma.Theranostics · 2026Article
- Therapeutic Use of Integrin Signaling in Melanoma Cells: Physical Link with the Extracellular Matrix (ECM).Cancers · 2025Review
- Integrins from extracellular vesicles as players in tumor microenvironment and metastasis.Cancer metastasis reviews · 2025Review
- Collagen in pituitary adenomas: A comprehensive review of biological roles and clinical implications.Journal of clinical & translational endocrinology · 2025Review
- Synthesis and Preclinical Evaluation of Dual-Targeted Molecular Tracer for Positron Emission Tomography Imaging of Programmed Cell Death Ligand‑1 and Integrin αACS pharmacology & translational science · 2025Article
- Dendrimer Conjugates with PD-L1-Binding Peptides Enhance In Vivo Antitumor Immune Response.Advanced healthcare materials · 2025Article
- Fibroblast Activation Protein (FAP)Oncogene · 2025Article
- Integrins in Cancer Drug Resistance: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2025Review
- A Review of Talin- and Integrin-Dependent Molecular Mechanisms in Cancer Invasion and Metastasis.International journal of molecular sciences · 2025Review
- Dual function antibody targeting αvβ3 and PD-L1 provide a promising strategy for solid tumor therapy.Frontiers in immunology · 2025Article
- Targeted inhibition of integrin αVβ3 induces cytotoxicity and suppresses migration ability in ovarian cancer cells and tumor spheroids.International journal of medical sciences · 2025Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumors utilize a number of effective strategies, including the programmed death 1/PD ligand 1 (PD-1/PD-L1) axis, to evade immune-mediated control of their growth. PD-L1 expression is mainly induced by IFN receptor signaling or constitutively induced. Integrins are an abundantly expressed class of proteins which play multiple deleterious roles in cancer and exert proangiogenic and prosurvival activities. We asked whether αvβ3-integrin positively regulates PD-L1 expression and the anticancer immune response. We report that αvβ3-integrin regulated constitutive and IFN-induced PD-L1 expression in human and murine cancerous and noncancerous cells. αvβ3-integrin targeted STAT1 through its signaling C tail. The implantation of β3-integrin-depleted tumor cells led to a dramatic decrease in the growth of primary tumors, which exhibited reduced PD-L1 expression and became immunologically hot, with increased IFNγ content and CD8+ cell infiltration. In addition, the implantation of β3-integrin-depleted tumors elicited an abscopal immunotherapeutic effect measured as protection from the challenge tumor and durable splenocyte and serum reactivity to B16 cell antigens. These modifications to the immunosuppressive microenvironment primed cells for checkpoint (CP) blockade. When combined with anti-PD-1, β3-integrin depletion led to durable therapy and elicited an abscopal immunotherapeutic effect. We conclude that in addition to its previously known roles, αvβ3-integrin serves as a critical component of the cancer immune evasion strategy and can be an effective immunotherapy target.
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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.