ArticleNature2017
CDK4/6 inhibition triggers anti-tumour immunity.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 938 papers, 3 of them syntheses that pooled it.
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.
PAveMenT: Phase Ib Study of Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer
Presurgical Treatment With Ribociclib and Letrozole in Patients With Locally Advanced Breast Cancer: the NEOLETRIB Study.
Who cites it
938 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,483 citations in OpenAlex.
- CDK4/6 inhibitors rechallenge post-progression in HR-positive HER2-negative advanced/metastatic breast cancer patients: a meta-analysis of Kaplan-Meier-reconstructed individual-level data.Breast cancer research : BCR · 2026Pooled it
- The Impact of Obesity on Treatment Outcomes in Patients with Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Receiving CDK 4/6 Inhibitors.Cancer research and treatment · 2026Pooled it
- CDK4/6 inhibitors as conditional immune-priming agents in breast cancer: therapeutic windows, sequencing strategies, and rational combinations with immunotherapy, radiotherapy, and antibody-drug conjugates.Frontiers in immunology · 2026Pooled it
- Phase 2 study of palbociclib plus retifanlimab in patients with advanced dedifferentiated liposarcoma.Journal for immunotherapy of cancer · 2026Trial
- Overall survival from the open-label phase II trial of palbociclib in patients with advanced well-differentiated/dedifferentiated liposarcoma.ESMO open · 2026Trial
- Palbociclib and endocrine therapy diminish adaptive anti-tumor immunity in early breast cancer: The NeoRHEA phase 2 study.Nature communications · 2025Trial
- Transcriptomic Predictors of Survival for Palbociclib + Endocrine Therapy Versus Capecitabine in Aromatase Inhibitor-Resistant Breast Cancer From the GEICAM/2013-02 PEARL Trial.JCO precision oncology · 2025Trial
- A Phase II Study of Abemaciclib for Patients with Retinoblastoma-Positive, Metastatic Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Determinants of response and molecular dynamics in HER2+ER+ breast cancers from the NA-PHER2 trial receiving HER2-targeted and endocrine therapies.Nature communications · 2025Trial
- Molecular mechanisms, current therapeutics, and emerging strategies in esophageal cancer: A comprehensive review.Chinese medical journal · 2026Review
- Targeting CDK2 ameliorates allergic asthma through suppression of epithelial chemokine production and T cell inflammatory responses.Science China. Life sciences · 2026Article
- Dynamic Immune Responsiveness in Breast Cancer: Tumor Microenvironment Plasticity, Therapeutic Timing, and Clinical Translation.International journal of molecular sciences · 2026Review
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Breast cancer immunogenicity as a spectrum: evolving concepts and therapeutic implications.The Journal of clinical investigation · 2026Review
- Avutometinib, Abemaciclib, and Fulvestrant in Patients with HR+/HER2- Metastatic Breast Cancer Previously Treated with CDK4/6 Inhibitor: A Single-Arm Phase I Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- CDK4/6 inhibitor-related interstitial lung disease in breast cancer: a single-center case series and literature-based patient-level review.Journal of thoracic disease · 2026Article
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- ATR inhibition induces NF-κB-dependent immunogenicity in Merkel cell carcinoma independent of cGAS-STING.NPJ precision oncology · 2026Article
- CDK4/6 inhibition induces a senescence-associated secretory phenotype via delayed NF-κB activation.Life science alliance · 2026Article
- Baseline and Early On-Treatment Prognostic Nutritional Index in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer Treated with CDK4/6 Inhibitors.Journal of clinical medicine · 2026Article
878 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are required for the initiation and progression of various malignancies. Pharmacological inhibitors of CDK4/6 have shown significant activity against several solid tumours. Their primary mechanism of action is thought to be the inhibition of phosphorylation of the retinoblastoma tumour suppressor, inducing G1 cell cycle arrest in tumour cells. Here we use mouse models of breast carcinoma and other solid tumours to show that selective CDK4/6 inhibitors not only induce tumour cell cycle arrest, but also promote anti-tumour immunity. We confirm this phenomenon through transcriptomic analysis of serial biopsies from a clinical trial of CDK4/6 inhibitor treatment for breast cancer. The enhanced anti-tumour immune response has two underpinnings. First, CDK4/6 inhibitors activate tumour cell expression of endogenous retroviral elements, thus increasing intracellular levels of double-stranded RNA. This in turn stimulates production of type III interferons and hence enhances tumour antigen presentation. Second, CDK4/6 inhibitors markedly suppress the proliferation of regulatory T cells. Mechanistically, the effects of CDK4/6 inhibitors both on tumour cells and on regulatory T cells are associated with reduced activity of the E2F target, DNA methyltransferase 1. Ultimately, these events promote cytotoxic T-cell-mediated clearance of tumour cells, which is further enhanced by the addition of immune checkpoint blockade. Our findings indicate that CDK4/6 inhibitors increase tumour immunogenicity and provide a rationale for new combination regimens comprising CDK4/6 inhibitors and immunotherapies as anti-cancer treatment.
Indexed as
Identifiers
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.