ArticleMolecular cell2021
Energy status dictates PD-L1 protein abundance and anti-tumor immunity to enable checkpoint blockade.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 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.
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Who cites it
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 238 citations in OpenAlex.
- Association of PD-L1 Expression with Clinicopathologic Characters in Gastric Cancer: A Comprehensive Meta-analysis.Current medicinal chemistry · 2024Pooled it
- PEOPLE (NTC03447678), a phase II trial to test pembrolizumab as first-line treatment in patients with advanced NSCLC with PD-L1 <50%: a multiomics analysis.Journal for immunotherapy of cancer · 2023Trial
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Nuclear OXCT1 attenuates histone β-hydroxybutyrylation-mediated MHC-I transcription.Nature chemical biology · 2026Article
- p53 hotspot mutants attenuate CTL-mediated tumor cell killing through a novel ALKBH5-YTHDF3-PD-L1 pathway.Oncogene · 2026Article
- Identification of lncRNAs in Breast Cancer Through Bioinformatics Analysis: Implications for Pathogenesis and Prognostic Significance.Cancer medicine · 2026Article
- AMPK as a central regulator of necroptosis: mechanistic insights and therapeutic implications.Journal of physiology and biochemistry · 2026Review
- PTX3 induces the expression of PD-L1 and promotes breast cancer immune escape.Breast cancer (Tokyo, Japan) · 2026Article
- Ketogenic Diet: A Metabolic Key to Overcoming Cancer Therapy Resistance.Molecular nutrition & food research · 2026Review
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Ketogenic Diet in Obesity and Diabetes: A Narrative Review.Nutrients · 2026Review
- Copper Depletion Nanoparticles Potentiate Cancer Immunotherapy by Avoiding Innate and Adaptive Immune Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Gut microbiota and cancer immunotherapy: from dysbiosis to personalized immune checkpoint blockade optimization.Folia microbiologica · 2026Review
- β-hydroxybutyrate potentiates anti-tumor immunity by modulating cytotoxic CD8Cancer immunology, immunotherapy : CII · 2026Article
- Targeting the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion.Cell reports. Medicine · 2026Article
- ROCK1 inhibition primes anti-tumor immunity in EGFR-mutant NSCLC by triggering PD-L1 degradation mediated by SMURF2.Molecular cancer · 2026Article
- Brain-targeting nanoplatform repurposing silymarin for enhanced GBM immunotherapy via synergistic mitochondrial suppression.Materials today. Bio · 2026Article
- Mitofusin-2 suppresses tumor immune escape through EGFR/STAT3-mediated PD-L1 transcription.Cell death & disease · 2026Article
- Review
87 more citing papers are in PubMed but not listed here.
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 6 institutions in 3 countries.
Funding
Abstract
Aberrant energy status contributes to multiple metabolic diseases, including obesity, diabetes, and cancer, but the underlying mechanism remains elusive. Here, we report that ketogenic-diet-induced changes in energy status enhance the efficacy of anti-CTLA-4 immunotherapy by decreasing PD-L1 protein levels and increasing expression of type-I interferon (IFN) and antigen presentation genes. Mechanistically, energy deprivation activates AMP-activated protein kinase (AMPK), which in turn, phosphorylates PD-L1 on Ser283, thereby disrupting its interaction with CMTM4 and subsequently triggering PD-L1 degradation. In addition, AMPK phosphorylates EZH2, which disrupts PRC2 function, leading to enhanced IFNs and antigen presentation gene expression. Through these mechanisms, AMPK agonists or ketogenic diets enhance the efficacy of anti-CTLA-4 immunotherapy and improve the overall survival rate in syngeneic mouse tumor models. Our findings reveal a pivotal role for AMPK in regulating the immune response to immune-checkpoint blockade and advocate for combining ketogenic diets or AMPK agonists with anti-CTLA4 immunotherapy to combat cancer.
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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.