ArticleNature cell biology2020
Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy.
Article in Nature cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04819958 (The Effect of Immunological Heterogeneity of Tumor Microenvironment in the Short-term Outcome and Long-term Outcome of Patients With Gastric Cancer), which is not on this map. Cited by 269 papers, 1 of them a synthesis that pooled it.
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
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.
The Effect of Immunological Heterogeneity of Tumor Microenvironment in the Short-term Outcome and Long-term Outcome of Patients With Gastric Cancer
Who cites it
269 citing papers in PubMed, 1 synthesis or guideline pooled it, 376 citations in OpenAlex.
- Efficacy and safety of PD-1 inhibitors plus chemotherapy for advanced unresectable gastroesophageal cancer: a systematic review and meta-analysis of phase III randomized controlled trials.Frontiers in oncology · 2026Pooled it
- Research progress on lysine acetylation (Review).International journal of molecular medicine · 2026Review
- The PD-L1-mTOR intersection in tumor migration and invasion.Molecular biology reports · 2026Review
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- ClonalLife science alliance · 2026Article
- PRKX-mediated stabilization of PD-L1 characterizes an immunosuppressive gastric cancer subtype.Journal for immunotherapy of cancer · 2026Article
- p53 hotspot mutants attenuate CTL-mediated tumor cell killing through a novel ALKBH5-YTHDF3-PD-L1 pathway.Oncogene · 2026Article
- Ubiquitin-driven regulation of immune checkpoints in lung cancer: Mechanisms and therapeutic implications (Review).Experimental and therapeutic medicine · 2026Review
- NAT10-Mediated ac4C Modification of circANKRD12 Reprograms the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- PD-L1 and PD-L2 regulate in cell-autonomous and N-glycosylation-dependent manners the pro-tumorigenic characteristics and functions of human cancer-associated fibroblasts.Molecular medicine (Cambridge, Mass.) · 2026Article
- Switchable Enzyme-Regulated ECM-Integrin-Cholesterol Signaling Orchestrate PD-L1 Dual Destabilization for Boosting Photo-Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Identifying membrane-bound transcriptional regulatory proteins from rare but evolutionarily conserved domain combinations.Nucleic acids research · 2026Article
- Genetic Interruption of PD-1/PD-L1 as an Alternative Means for Immune Checkpoint Blockade in Cancer: A Review.Pharmaceutics · 2026Review
- Nuclear PD-L1: an emerging oncogenic driver and promising therapeutic target in cancer.Journal of biomedical science · 2026Review
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma.Molecular oncology · 2026Article
- Targeting CAFs-derived PCSK6 inhibits redistribution of PD-L1 and restores response of CD8Cell death and differentiation · 2026Article
- Immunotherapy in Thyroid Cancer: Current Strategies and Challenges.Cancer medicine · 2026Review
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
209 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 8 institutions in 3 countries.
Funding
Abstract
Immunotherapies that target programmed cell death protein 1 (PD-1) and its ligand PD-L1 as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) have shown impressive clinical outcomes for multiple tumours. However, only a subset of patients achieves durable responses, suggesting that the mechanisms of the immune checkpoint pathways are not completely understood. Here, we report that PD-L1 translocates from the plasma membrane into the nucleus through interactions with components of the endocytosis and nucleocytoplasmic transport pathways, regulated by p300-mediated acetylation and HDAC2-dependent deacetylation of PD-L1. Moreover, PD-L1 deficiency leads to compromised expression of multiple immune-response-related genes. Genetically or pharmacologically modulating PD-L1 acetylation blocks its nuclear translocation, reprograms the expression of immune-response-related genes and, as a consequence, enhances the anti-tumour response to PD-1 blockade. Thus, our results reveal an acetylation-dependent regulation of PD-L1 nuclear localization that governs immune-response gene expression, and thereby advocate targeting PD-L1 translocation to enhance the efficacy of PD-1/PD-L1 blockade.
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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.