ArticleScience (New York, N.Y.)2016
Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity.
Registry-linked trialAbstract read
In one paragraph
Article in Science (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03220178 (PRECYCLE), which is not on this map. Cited by 206 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
206citing papers in PubMed, 1 pooled it
18.3field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
PRECYCLE: Multicenter, Randomized Phase IV Intergroup Trial to Evaluate the Impact of eHealth-based Patient Reported Outcome (PRO) Assessment on Quality of Life in Patients With Hormone Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer Treated With Palbociclib and an Aromatase Inhibitor- or Palbociclib and Fulvestrant
Who cites it
206 citing papers in PubMed, 1 synthesis or guideline pooled it, 309 citations in OpenAlex.
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.International journal of molecular sciences · 2021Pooled it
- Local delivery of interferon restores antigen presentation and sensitizes medulloblastoma to T cell killing.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- The Role of Transcriptional and Atypical Cyclin-Dependent Protein Kinases in Melanoma.Cancers · 2026Review
- Drugging non-canonical kinases in cancer therapeutics: Molecular targets, underlying mechanisms and small-molecule inhibitors.Acta pharmaceutica Sinica. B · 2026Review
- Article
- Cuproptosis and Disulfidptosis Converge to Empower PD-L1 Checkpoint Therapy via Cadict-Induced PD-L1 Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Interferon Regulatory Factor 2 (IRF2) Suppression Enhances Murine Cardiac Allograft Survival Through Immune Evasion.Immunology · 2026Article
- Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Immune checkpoint inhibition in breast cancer: targeting PD-1/PD-L1 pathway for therapeutic advances.Breast cancer (Tokyo, Japan) · 2026Review
- Decoding the immune microenvironment: precision immunotherapy for medulloblastoma subtypes.Frontiers in immunology · 2026Review
- A 3'UTR polymorphism disrupts IRF2BP2 autoregulation through an eIF4H translational enhancer.Frontiers in genetics · 2026Article
- The roles of cell cycle proteins in regulating the tumor immune microenvironment.Genes & diseases · 2026Review
- The Duality of Cdk5: A Master Regulator in Neurodevelopment and a Hijacked Oncogene in Cancer.Cells · 2025Review
- Structural immunotherapy: Harnessing chemical design to build powerful next-generation therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Multifaceted Role of Osteopontin in Modulating the Tumor Microenvironment.Cancer research · 2025Review
- Application of Gene Editing Technology Based on Targeted Delivery Materials in TNBC.ACS omega · 2025Review
- Emerging new immune checkpoint inhibitors in solid tumor immunotherapy.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Review
- Ferroptosis: CD8Cell death discovery · 2025Review
146 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
12 authors at 2 institutions in 1 country.
R Dixon DorandDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Division of Pediatric Hematology-Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Joseph NthaleDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Angie Fowler Adolescent and Young Adult Cancer Institute and University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA.
Jay T MyersDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Angie Fowler Adolescent and Young Adult Cancer Institute and University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA.
Deborah S BarkauskasDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Angie Fowler Adolescent and Young Adult Cancer Institute and University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA.
Stefanie AvrilDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Steven M ChirieleisonDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Tej K PareekDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Angie Fowler Adolescent and Young Adult Cancer Institute and University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA.
Derek W AbbottDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Duncan S StearnsDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Angie Fowler Adolescent and Young Adult Cancer Institute and University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
John J LetterioDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Angie Fowler Adolescent and Young Adult Cancer Institute and University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Alex Y HuangDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Division of Pediatric Hematology-Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Angie Fowler Adolescent and Young Adult Cancer Institute and University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. ayh3@case.edu axp125@case.edu.
Agne PetrosiuteDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Angie Fowler Adolescent and Young Adult Cancer Institute and University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. ayh3@case.edu axp125@case.edu.
Case Western Reserve University · USUniversity School · US
Funding
TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARK R CHANCE · 1987 to 2026
$142.3MClinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4MUbiquitination Pathways Mediating Chronic Intestinal InflammationP01DK091222 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI PIZARRO, THERESA TORRES · 2011 to 2020
$16.5MThe Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI Theresa Torres Pizarro · 2015 to 2026
$15.6MClinical and Translational Science Collaborative of ClevelandKL2TR000440 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$11.1MInnate Immune Signal Transduction Specificity in Inflammatory DiseaseR01GM086550 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI ABBOTT, DEREK W · 2009 to 2020
$3.8MImmunology Training Program-PredoctoralT32AI089474 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI COBB, BRIAN A · 2010 to 2025
$3.4MComprehensive Training Program in Imaging Science and InformaticsT32EB007507 · NIBIB · UNIVERSITY OF TEXAS AT AUSTIN · PI MARKEY, MIA K, RYLANDER, HENRY GRADY · 2009 to 2024
$2.7MMechanistic Dynamic Study of Intranodal Chemokine-aided Antitumor Immune PrimingR01CA154656 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 2011 to 2015
$1.7MNovel mechanisms of immune activation following allogeneic, hematopoietic stem cell transplantationR01HL111682 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI COOKE, KENNETH R, LETTERIO, JOHN JAMES · 2013 to 2016
$1.6MCdk5 signaling in ICN1-induced T Cell LeukemogenesisR21CA181875 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN, LETTERIO, JOHN JAMES · 2015 to 2016
$379kNCATS NIH HHS KL2 TR000440NCATS NIH HHS KL2TR000440NCATS NIH HHS UL1 TR000439NCATS NIH HHS UL1TR000439NCI NIH HHS F31 CA196265NCI NIH HHS F31CA196265NCI NIH HHS P30 CA043703NCI NIH HHS P30CA043703NCI NIH HHS R01 CA154656NCI NIH HHS R01CA154656NCI NIH HHS R21 CA181875NCI NIH HHS R21CA181875NHLBI NIH HHS R01 HL111682NHLBI NIH HHS R01HL111682NIAID NIH HHS T32 AI089474NIAID NIH HHS T32AI089474NIBIB NIH HHS T32 EB007507NIDDK NIH HHS P01 DK091222NIDDK NIH HHS P30 DK097948NIGMS NIH HHS R01 GM086550NIGMS NIH HHS R01GM086550NIGMS NIH HHS T32 GM007250NIGMS NIH HHS T32GM007250
Abstract
Cancers often evade immune surveillance by adopting peripheral tissue- tolerance mechanisms, such as the expression of programmed cell death ligand 1 (PD-L1), the inhibition of which results in potent antitumor immunity. Here, we show that cyclin-dependent kinase 5 (Cdk5), a serine-threonine kinase that is highly active in postmitotic neurons and in many cancers, allows medulloblastoma (MB) to evade immune elimination. Interferon-γ (IFN-γ)-induced PD-L1 up-regulation on MB requires Cdk5, and disruption of Cdk5 expression in a mouse model of MB results in potent CD4(+) T cell-mediated tumor rejection. Loss of Cdk5 results in persistent expression of the PD-L1 transcriptional repressors, the interferon regulatory factors IRF2 and IRF2BP2, which likely leads to reduced PD-L1 expression on tumors. Our finding highlights a central role for Cdk5 in immune checkpoint regulation by tumor cells.
Indexed as
Gene Expression Regulation, NeoplasticAnimalsB7-H1 AntigenCD4-Positive T-LymphocytesCell Line, TumorCerebellar NeoplasmsCyclin-Dependent Kinase 5HumansImmunologic SurveillanceInterferon Regulatory Factor-2MaleMedulloblastomaMiceMice, Inbred C57BLMice, NudeNeoplasms, ExperimentalB7-H1 AntigenCd274 protein, mouseCdk5 protein, mouseCyclin-Dependent Kinase 5Interferon Regulatory Factor-2IRF2BP2 protein, mouseIrf2 protein, mouseTranscription Factors
Identifiers
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Read underepoch 390
Registered trials
NCT03220178ClinicalTrials.gov
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.