ArticleJournal for immunotherapy of cancer2023
Dendritic cell therapy augments antitumor immunity triggered by CDK4/6 inhibition and immune checkpoint blockade by unleashing systemic CD4 T-cell responses.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 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
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- Tumors located in the brain impair the frequency and phenotype of dendritic cells in blood and tumor.iScience · 2026Article
- Immune evasion driven by lipid metabolic reprogramming in endocrine-resistant HRFrontiers 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
- The landscape of cyclin-dependent kinase 4/6 inhibitors in solid malignancies: emphasis on immunotherapy combinatorial strategies.Medical oncology (Northwood, London, England) · 2025Review
- The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- Myeloid cells meet CD8Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Identification of CDK4/6 Inhibitors as Small Molecule NLRP3 Inflammasome Activators that Facilitate IL-1β Secretion and T Cell Adjuvanticity.Journal of medicinal chemistry · 2024Article
- Recent progress of CDK4/6 inhibitors' current practice in breast cancer.Cancer gene therapy · 2024Review
- The complex interplay of tumor-infiltrating cells in driving therapeutic resistance pathways.Cell communication and signaling : CCS · 2024Review
- Article
- Functional analysis and validation of oncodrive gene AP3S1 in ovarian cancer through filtering of mutation data from whole-exome sequencing.European journal of medical research · 2024Article
- A bibliometric analysis of drug resistance in immunotherapy for breast cancer: trends, themes, and research focus.Frontiers in immunology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are a mainstay treatment for hormone receptor-positive breast cancer. While their principal mechanism is inhibition of cancer cell proliferation, preclinical and clinical evidence suggests that CDK4/6i can also promote antitumor T-cell responses. However, this pro-immunogenic property is yet to be successfully harnessed in the clinic, as combining CDK4/6i with immune checkpoint blockade (ICB) has not shown a definitive benefit in patients.
methodWe performed an in-depth analysis of the changes in the tumor immune microenvironment and systemic immune modulation associated with CDK4/6i treatment in muring breast cancer models and in patients with breast cancer using high dimensional flow cytometry and RNA sequencing. Gain and loss of function in vivo experiments employing cell transfer and depletion antibody were performed to uncover immune cell populations critical for CDK4/6i-mediated stimulation of antitumor immunity.
resultsWe found that loss of dendritic cells (DCs) within the tumor microenvironment resulting from CDK4/6 inhibition in bone marrow progenitors is a major factor limiting antitumor immunity after CDK4/6i and ICB. Consequently, restoration of DC compartment by adoptively transferring ex vivo differentiated DCs to mice treated with CDK4/6i and ICB therapy enabled robust tumor inhibition. Mechanistically, the addition of DCs promoted the induction of tumor-localized and systemic CD4 T-cell responses in mice receiving CDK4/6i-ICB-DC combination therapy, as characterized by enrichment of programmed cell death protein-1-negative T helper (Th)1 and Th2 cells with an activated phenotype. CD4 T-cell depletion abrogated the antitumor benefit of CDK4/6i-ICB-DC combination, with outgrowing tumors displaying an increased proportion of terminally exhausted CD8 T cells.
conclusionsOur findings suggest that CDK4/6i-mediated DC suppression limits CD4 T-cell responses essential for the sustained activity of CD8 T cells and tumor inhibition. Furthermore, they imply that restoring DC-CD4 T-cell crosstalk via DC transfer enables effective breast cancer immunity in response to CDK4/6i and ICB 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.