ArticleJournal for immunotherapy of cancer2021
Orphan nuclear receptor TLX promotes immunosuppression via its transcriptional activation of PD-L1 in glioma.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- RNA Expression Signatures in Glioblastoma: A Systematic Review of Tumour Biology and Therapeutic Targets.Oncology research · 2025Pooled it
- Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma.Molecular cancer · 2023Trial
- GITR activation potentiates anti-tumor immunity of tumor-infiltrating lymphocytes expanded from glioblastoma by rescuing exhaustion.Oncogene · 2026Article
- scCirclehunter delineates ecDNA-containing cells using single-cell ATAC-seq, with a focus on glioblastoma.Cell discovery · 2025Article
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Article
- Harnessing innate immunity against glioblastoma microenvironment.Frontiers in immunology · 2025Review
- Prognostic significance and multivariate modeling of COL4A family genes and HMGA2 in glioma.Frontiers in pharmacology · 2025Article
- Nuclear receptor TLX functions to promote cancer stemness and EMT in prostate cancer via its direct transactivation of CD44 and stem cell-regulatory transcription factors.British journal of cancer · 2024Article
- Exploring the prognostic value of BRMS1 + microglia based on single-cell anoikis regulator patterns in the immunologic microenvironment of GBM.Journal of neuro-oncology · 2024Article
- ALOX5 contributes to glioma progression by promoting 5-HETE-mediated immunosuppressive M2 polarization and PD-L1 expression of glioma-associated microglia/macrophages.Journal for immunotherapy of cancer · 2024Article
- IGFBP3 induces PD-L1 expression to promote glioblastoma immune evasion.Cancer cell international · 2024Article
- Interaction, immune infiltration characteristics and prognostic modeling of efferocytosis-related subtypes in glioblastoma.BMC medical genomics · 2023Article
- Advances in research on immune escape mechanism of glioma.CNS neuroscience & therapeutics · 2023Review
- PERK-Mediated Cholesterol Excretion from IDH Mutant Glioma Determines Anti-Tumoral Polarization of Microglia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Regulation of PD-L1 Expression by Nuclear Receptors.International journal of molecular sciences · 2023Review
- Combining single-cell sequencing and spatial transcriptome sequencing to identify exosome-related features of glioblastoma and constructing a prognostic model to identify BARD1 as a potential therapeutic target for GBM patients.Frontiers in immunology · 2023Article
- Tripartite motif-containing 25 facilitates immunosuppression and inhibits apoptosis of glioma via activating NF-κB.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Large-Scale Single-Cell and Bulk Sequencing Analyses Reveal the Prognostic Value and Immune Aspects of CD147 in Pan-Cancer.Frontiers in immunology · 2022Article
- INPP4B inhibits glioma cell proliferation and immune escapeFrontiers in oncology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh-grade gliomas are rapidly progressing tumors of the central nervous system, and are associated with poor prognosis and highly immunosuppressive microenvironments. Meanwhile, a better understanding of PD-L1, a major prognostic biomarker for checkpoint immune therapy, regulation may provide insights for developing novel immunotherapeutic strategies for treating gliomas. In the present study, we elucidate the functional significance of the orphan nuclear receptor TLX in human glioma, and its functional role in immune suppression through regulation of PD-L1/PD-1 axis.
methodsTLX and PD-L1 expression patterns, and their association with clinicopathological parameters and immune phenotypes of glioma were analysed using CIBERSORT algorithm and single-sample gene-set enrichment analysis from The Cancer Genome Atlas (n=695) and Chinese Glioma Genome Atlas (n=1018) databases. Protein expression and cellular localization of TLX, PD-L1, and PD-1, as well as the prevalence of cytotoxic tumor-infiltrating lymphocytes (TILs), and tumor-associated macrophages (TAMs), in the glioma immune microenvironment were analyzed via tissue microarray by immunohistochemistry and multiplex immunofluorescence. Glioma allografts and xenografts with TLX manipulation (knockdown/knockout or reverse agonist) were inoculated subcutaneously, or orthotopically into the brains of immunodeficient and immunocompetent mice to assess tumor growth by imaging, and the immune microenvironment by flow cytometry. PD-L1 transcriptional regulation by TLX was analyzed by chromatin immunoprecipitation and luciferase reporter assays.
resultsTLX and PD-L1 expression was positively associated with macrophage-mediated immunosuppressive phenotypes in gliomas. TLX showed significant upregulation and positive correlation with PD-L1. Meanwhile, suppression of TLX significantly inhibited
conclusionsTLX contributes to glioma malignancy and immunosuppression through transcriptional activation of PD-L1 ligands that bind to PD-1 expressed on both TILs and TAMs. Thus, targeting the druggable TLX may have potential therapeutic significance in glioma immune therapy.
Indexed as
Identifiers
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.