ArticleThe Journal of clinical investigation2023
PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The trial behind it
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Who cites it
43 citing papers in PubMed, 49 citations in OpenAlex.
- PD-1/PD-L1 Signaling in Non-ICI Myocarditis.JACC. Basic to translational science · 2026Article
- Repurposed ethoxzolamide reprograms antitumor immunity through β-TrCP-dependent PD-L1 ubiquitination.Cell reports. Medicine · 2026Article
- Cinnamon-Derived Compounds Reduce PD-L1 Expression in UV-Exposed Human Skin Cell Line.Medicines (Basel, Switzerland) · 2026Article
- Nuclear PD-L1: an emerging oncogenic driver and promising therapeutic target in cancer.Journal of biomedical science · 2026Review
- Targeting CAFs-derived PCSK6 inhibits redistribution of PD-L1 and restores response of CD8Cell death and differentiation · 2026Article
- Downregulation of B7-H4 contributes to the synergistic effect of USP2a-targeted/anti-PD-1 combination therapy in EGFR mutant lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Ceramide disrupts TM9SF2-PGK1 axis to redirect PD-L1 trafficking and enhance antitumor immunity.Nature communications · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Research progress ofFrontiers in immunology · 2026Review
- The primary cilium as a compartmentalized signaling hub in tissue immunity and homeostasis.Frontiers in cell and developmental biology · 2026Review
- Monoclonal Antibodies and Derivatives: Therapeutic Tools for Cancer.Oncology research · 2026Review
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- Targeted destruction of VISTA boosts anti-tumor immunotherapy.Cell research · 2025Article
- Non-Histone Lysine Modifications in Tumor Microenvironment: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- PD-1/PD-L1 Cancer Immunotherapeutics Reshape Tumor Microenvironment - Clinical Evidence and Molecular Mechanisms for AI-based Precision Medicine.Clinical reviews in allergy & immunology · 2025Review
- Human CD24+CD38+ regulatory B cells promote pro-resolving macrophage function through the synergistic effect of IL-10 and PD-L1.Journal of leukocyte biology · 2025Article
- Biochemical analysis of PD-L1 ubiquitination by CRL3Structure (London, England : 1993) · 2025Article
- p53/PD-L1 co-expression predicts poor prognosis in diffuse large B-cell lymphoma.Discover oncology · 2025Article
- Identification and validation of a thirteen-gene signature based on ubiquitin related genes in cervical cancer.Discover oncology · 2025Article
- cIAP2-mediated IGF2BP2 ubiquitination and degradation regulate cardiomyocyte apoptosis via stabilizing mCell biology and toxicology · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Programmed death-ligand 1 (PD-L1), a critical immune checkpoint ligand, is a transmembrane protein synthesized in the endoplasmic reticulum of tumor cells and transported to the plasma membrane to interact with programmed death 1 (PD-1) expressed on T cell surface. This interaction delivers coinhibitory signals to T cells, thereby suppressing their function and allowing evasion of antitumor immunity. Most companion or complementary diagnostic devices for assessing PD-L1 expression levels in tumor cells used in the clinic or in clinical trials require membranous staining. However, the mechanism driving PD-L1 translocation to the plasma membrane after de novo synthesis is poorly understood. Herein, we showed that mind bomb homolog 2 (MIB2) is required for PD-L1 transportation from the trans-Golgi network (TGN) to the plasma membrane of cancer cells. MIB2 deficiency led to fewer PD-L1 proteins on the tumor cell surface and promoted antitumor immunity in mice. Mechanistically, MIB2 catalyzed nonproteolytic K63-linked ubiquitination of PD-L1, facilitating PD-L1 trafficking through Ras-associated binding 8-mediated (RAB8-mediated) exocytosis from the TGN to the plasma membrane, where it bound PD-1 extrinsically to prevent tumor cell killing by T cells. Our findings demonstrate that nonproteolytic ubiquitination of PD-L1 by MIB2 is required for its transportation to the plasma membrane and tumor cell immune evasion.
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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.