ArticleOncotarget2017
A regulatory role for the co-chaperone FKBP51s in PD-L1 expression in glioma.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 96 citations in OpenAlex.
- Combining Magnetic Resonance Imaging with Systemic Monocyte Evaluation for the Implementation of GBM Management.International journal of molecular sciences · 2021Trial
- A delayed translocation into the endoplasmic reticulum controls the post-translational modifications of PD-L1.Nature communications · 2026Article
- FKBP5 isoforms shape immune pathways related to tumor tolerance.Cell death discovery · 2026Article
- Intracellular PD-L1: Functions, Regulation, and Therapeutic Implications.International journal of biological sciences · 2026Review
- Review
- Comprehensive analysis of heat shock proteins in glioma revealed the association with glioma-associated myeloid cells.Genes and immunity · 2025Article
- Soluble PD-L1: From Immune Evasion to Cancer Therapy.Life (Basel, Switzerland) · 2025Review
- Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy.Experimental hematology & oncology · 2025Review
- The potential impact of RNA splicing abnormalities on immune regulation in endometrial cancer.Cell death & disease · 2025Review
- Role of FK506 binding protein 51 in central nervous system diseases.Frontiers in molecular neuroscience · 2025Review
- Differential Dynamics and Roles of FKBP51 Isoforms and Their Implications for Targeted Therapies.International journal of molecular sciences · 2024Article
- GFPT1 accelerates immune escape in breast cancer by modifying PD-L1 via O-glycosylation.BMC cancer · 2024Article
- Regulation of post-translational modification of PD-L1 and associated opportunities for novel small-molecule therapeutics.Future medicinal chemistry · 2024Review
- N-linked glycosylation of PD-L1/PD-1: an emerging target for cancer diagnosis and treatment.Journal of translational medicine · 2024Review
- Glycosylation and Its Role in Immune Checkpoint Proteins: From Molecular Mechanisms to Clinical Implications.Biomedicines · 2024Review
- The FKBP51s Splice Isoform Predicts Unfavorable Prognosis in Patients with Glioblastoma.Cancer research communications · 2024Article
- Emerging therapeutic frontiers in cancer: insights into posttranslational modifications of PD-1/PD-L1 and regulatory pathways.Experimental hematology & oncology · 2024Review
- Challenges Coexist with Opportunities: Spatial Heterogeneity Expression of PD-L1 in Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- HSP90 multi-functionality in cancer.Frontiers in immunology · 2024Review
- Optimization of cancer immunotherapy on the basis of programmed death ligand-1 distribution and function.British journal of pharmacology · 2024Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFKBP51 is a co-chaperone with isomerase activity, abundantly expressed in glioma. We previously identified a spliced isoform (FKBP51s) and highlighted a role for this protein in the upregulation of Programmed Death Ligand 1 (PD-L1) expression in melanoma. Because gliomas can express PD-L1 causing a defective host anti-tumoral immunity, we investigated whether FKBP51s was expressed in glioma and played a role in PD-L1 regulation in this tumour.
methodsWe used D54 and U251 glioblastoma cell lines that constitutively expressed PD-L1. FKBP51s was measured by immunoblot, flow cytometry and microscopy. In patient tumours, IHC and qPCR were used to measure protein and mRNA levels respectively. FKBP51s depletion was achieved by siRNAs, and its enzymatic function was inhibited using selective inhibitors (SAFit). We investigated protein maturation using N-glycosidase and cell fractionation approaches.
resultsFKBP51s was expressed at high levels in glioma cells. Glycosylated-PD-L1 was increased and reduced by FKBP51s overexpression or silencing, respectively. Naïve PD-L1 was found in the endoplasmic reticulum (ER) of glioma cells complexed with FKBP51s, whereas the glycosylated form was measured in the Golgi apparatus. SAFit reduced PD-L1 levels (constitutively expressed and ionizing radiation-induced). SAFit reduced cell death of PBMC co-cultured with glioma.
conclusionsHere we addressed the mechanism of post-translational regulation of PD-L1 protein in glioma. FKBP51s upregulated PD-L1 expression on the plasma membrane by catalysing the protein folding required for subsequent glycosylation. Inhibition of FKBP51s isomerase activity by SAFit decreased PD-L1 levels. These findings suggest that FKBP51s is a potential target of immunomodulatory strategies for glioblastoma treatment.
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