ArticleOncoimmunology2021
Low-dose CDK4/6 inhibitors induce presentation of pathway specific MHC ligands as potential targets for cancer immunotherapy.
Article in Oncoimmunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- 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 I/II trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer.European journal of cancer (Oxford, England : 1990) · 2021Trial
- Aberrant SUMOylation Restricts the Targetable Cancer Immunopeptidome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Drug Repurposing in Oncology: A Strategic Pathway to Unlocking New Therapeutic Potential.Therapeutic innovation & regulatory science · 2026Review
- Cyclin-dependent kinase 4 and 6 inhibitors and the breast cancer immune ecosystem: immune remodeling, resistance, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- The Dual Effects of CDK4/6 Inhibitors on Tumor Immunity.Cancers · 2025Review
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- A narrative review of therapy-induced senescence in cancer: mechanisms, immune interplay, and therapeutic opportunities.Journal of the Egyptian National Cancer Institute · 2025Review
- Review
- Targeting CDK4/6 in breast cancer.Experimental & molecular medicine · 2025Review
- Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives.Bioengineering (Basel, Switzerland) · 2024Review
- Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Targeting Proteasomes and the MHC Class I Antigen Presentation Machinery to Treat Cancer, Infections and Age-Related Diseases.Cancers · 2023Review
- Host Interactions with Engineered T-cell Micropharmacies.Cancer immunology research · 2023Article
- A review on the role of cyclin dependent kinases in cancers.Cancer cell international · 2022Review
- Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment.Nature reviews. Drug discovery · 2022Review
- IFN-γ and TNF Induce Senescence and a Distinct Senescence-Associated Secretory Phenotype in Melanoma.Cells · 2022Article
- Novel sequential therapy with metformin enhances the effects of cisplatin in testicular germ cell tumours via YAP1 signalling.Cancer cell international · 2022Article
- AKT1 Is Required for a Complete Palbociclib-Induced Senescence Phenotype in BRAF-V600E-Driven Human Melanoma.Cancers · 2022Article
- The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cyclin dependent kinase 4/6 inhibitors (CDK4/6i) lead to cell-cycle arrest but also trigger T cell-mediated immunity, which might be mediated by changes in human leukocyte antigen (HLA) ligands. We investigated the effects of CDK4/6i, abemaciclib and palbociclib, on the immunopeptidome at nontoxic levels in breast cancer cell lines by biochemical identification of HLA ligands followed by network analyses. This treatment led to upregulation of HLA and revealed hundreds of induced HLA ligands in breast cancer cell lines. These new ligands were significantly enriched for peptides derived from proteins involved in the "G1/S phase transition of cell cycle" including HLA ligands from CDK4/6, Cyclin D1 and the 26S regulatory proteasomal subunit 4 (PSMC1). Interestingly, peptides from proteins targeted by abemaciclib and palbociclib, were predicted to be the most likely to induce a T cell response. In strong contrast, peptides induced by solely one of the drugs had a lower T cell recognition score compared to the DMSO control suggesting that the observed effect is class dependent. This general hypothesis was exemplified by a peptide from PSMC1 which was among the HLA ligands with highest prediction scores and which elicited a T cell response in healthy donors. Overall, these data demonstrate that CDK4/6i treatment gives rise to drug-induced HLA ligands from G1/S phase transition, that have the highest chance for being recognized by T cells, thus providing evidence that inhibition of a distinct cellular process leads to increased presentation of the involved proteins that may be targeted by immunotherapeutic agents.
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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.