ArticleJournal for immunotherapy of cancer2021
THADA drives Golgi residency and upregulation of PD-L1 in cancer cells and provides promising target for immunotherapy.
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. An erratum has been issued. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Pathophysiological Roles of Two Intracellular P-Type ATPases: The Cancer-Associated NaInternational journal of molecular sciences · 2026Review
- TMEM131-Mediated Soluble TRAIL Triggered Type II Alveolar Epithelial Cell Senescence in Radiation-Induced Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Twin pairs discordant for incident coronary artery disease reveal epigenetic and transcriptomic differences by gene region.Molecular genetics and genomics : MGG · 2025Article
- Structural insights into tRNA recognition of the human FTSJ1-THADA complex.Communications biology · 2025Article
- Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Zosuquidar Promotes Antitumor Immunity by Inducing Autophagic Degradation of PD-L1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Beyond inhibition against the PD-1/PD-L1 pathway: development of PD-L1 inhibitors targeting internalization and degradation of PD-L1.RSC medicinal chemistry · 2024Review
- Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect.The journal of physiological sciences : JPS · 2024Article
- HTRA1-driven detachment of type I collagen from endoplasmic reticulum contributes to myocardial fibrosis in dilated cardiomyopathy.Journal of translational medicine · 2024Article
- Article
- Challenges Coexist with Opportunities: Spatial Heterogeneity Expression of PD-L1 in Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- THADA inhibits autophagy and increases 5-FU sensitivity in gastric cancer cells via the PI3K/AKT/mTOR signaling pathway.Iranian journal of basic medical sciences · 2024Article
- Drug repositioning in thyroid cancer: from point mutations to gene fusions.Frontiers in oncology · 2024Review
- Vesicle-mediated transport-related genes predict the prognosis and immune microenvironment in hepatocellular carcinoma.Journal of Cancer · 2024Article
- USP2 promotes tumor immune evasion via deubiquitination and stabilization of PD-L1.Cell death and differentiation · 2023Article
- The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- How the interplay among the tumor microenvironment and the gut microbiota influences the stemness of colorectal cancer cells.World journal of stem cells · 2023Review
- PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination.The Journal of clinical investigation · 2023Article
- Identification of a Trm732 Motif Required for 2'-ACS omega · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe abnormal upregulation of programmed death-ligand 1 (PD-L1) in cancer cells inhibits T cell-mediated cytotoxicity, but the molecular mechanisms that drive and maintain PD-L1 expression are still incompletely understood.
methodsCombined analyses of genomes and proteomics were applied to find potential regulators of PD-L1. In vitro experiments were performed to investigate the regulatory mechanism of PD-L1 by thyroid adenoma associated gene (THADA) using human colorectal cancer (CRC) cells. The prevalence of THADA was analyzed using CRC tissue microarrays by immunohistochemistry. T cell killing assay, programmed cell death 1 binding assay and MC38 transplanted tumor models in C57BL/6 mice were developed to investigate the antitumor effect of THADA.
resultsTHADA is critically required for the Golgi residency of PD-L1, and this non-redundant, coat protein complex II (COPII)-associated mechanism maintains PD-L1 expression in tumor cells. THADA mediated the interaction between PD-L1 as a cargo protein with SEC24A, a module on the COPII trafficking vesicle. Silencing THADA caused absence and endoplasmic reticulum (ER) retention of PD-L1 but not major histocompatibility complex-I, inducing PD-L1 clearance through ER-associated degradation. Targeting THADA substantially enhanced T cell-mediated cytotoxicity, and increased CD8+ T cells infiltration in mouse tumor tissues. Analysis on clinical tissue samples supported a potential role of THADA in upregulating PD-L1 expression in cancer.
conclusionsOur data reveal a crucial cellular process for PD-L1 maturation and maintenance in tumor cells, and highlight THADA as a promising target for overcoming PD-L1-dependent immune evasion.
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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.