ArticleCancer research2022
Phosphorylation and Stabilization of PD-L1 by CK2 Suppresses Dendritic Cell Function.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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
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Who cites it
35 citing papers in PubMed, 45 citations in OpenAlex.
- ClonalLife science alliance · 2026Article
- CK2 in triple-negative breast cancer: oncogenic signaling networks and emerging CK2 inhibitor-based combination therapies.Clinical and experimental medicine · 2026Review
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- Inhibition of protein kinase CK2 remodels the tumor immune microenvironment and sensitizes lung cancer to PD-L1 blockade.Experimental hematology & oncology · 2026Article
- HE4 drives PD-L1 expression in myeloid cells via IFN-γR-JAK-STAT3 signaling to promote tumor immune evasion.Cell reports. Medicine · 2026Article
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- Engineered Fenretinide- and Tocilizumab-Releasing Janus Nanoparticles for Site-Directed Immunochemoprevention of Squamous Cell Carcinoma of the Lung.Pharmaceutics · 2025Article
- Kinome-Wide Screening Identifies FAK as a Novel Post-Translational Regulator of PD-L1 Stability and Immune Evasion in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Article
- Ubiquitination in cancer: mechanisms and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- Biochemical analysis of PD-L1 ubiquitination by CRL3Structure (London, England : 1993) · 2025Article
- Progress in understanding the regulatory mechanisms of immune checkpoint proteins PD-1 and PD-L1 expression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- CK2 in the spotlight: decoding its role in hematological malignancies and therapeutic applications.Discover oncology · 2025Review
- NADAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pyroptosis in cardiovascular diseases: molecular mechanisms, pathological roles, and therapeutic implications.American journal of cardiovascular disease · 2025Review
- FBXO9 promotes anti-tumor immunity via degradation of PD-L1 in pancreatic cancer.Frontiers in immunology · 2025Article
- Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.Experimental hematology & oncology · 2024Review
- Regulation of post-translational modification of PD-L1 and associated opportunities for novel small-molecule therapeutics.Future medicinal chemistry · 2024Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
Targeting immune checkpoints such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has transformed cancer treatment, with durable clinical responses across a wide range of tumor types. However, a high percentage of patients fail to respond to anti-PD-1/PD-L1 treatment. A greater understanding of PD-L1 regulation is critical to improving the clinical response rate of PD-1/PD-L1 blockade. Here, we demonstrate that PD-L1 is phosphorylated and stabilized by casein kinase 2 (CK2) in cancer and dendritic cells (DC). Phosphorylation of PD-L1 at Thr285 and Thr290 by CK2 disrupted PD-L1 binding with speckle-type POZ protein, an adaptor protein of the cullin 3 (CUL3) ubiquitin E3 ligase complex, protecting PD-L1 from CUL3-mediated proteasomal degradation. Inhibition of CK2 decreased PD-L1 protein levels by promoting its degradation and resulted in the release of CD80 from DC to reactivate T-cell function. In a syngeneic mouse model, combined treatment with a CK2 inhibitor and an antibody against T-cell immunoglobulin mucin-3 (Tim-3) suppressed tumor growth and prolonged survival. These findings uncover a mechanism by which PD-L1 is regulated and suggest a potential antitumor treatment option to activate DC function by blocking the CK2-PD-L1 pathway and inhibiting Tim-3. SIGNIFICANCE: This work identifies a role for CK2 in immunosuppression by phosphorylation and stabilization of PD-L1, identifying CK2 inhibition as an immunotherapeutic approach for treating cancer.
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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.