ArticlePLoS computational biology2022
Dose-dependent thresholds of dexamethasone destabilize CAR T-cell treatment efficacy.
Article in PLoS computational biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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
18 citing papers in PubMed, 23 citations in OpenAlex.
- Emerging frontiers in adoptive cell therapies: engineering innovations, current challenges, and manufacturing perspectives.Molecular biology reports · 2026Review
- Prophylactic dexamethasone at the time of absolute lymphocyte expansion does not mitigate risk or event-free survival for immune effector cell associated delayed neurotoxicity.Blood cancer journal · 2026Article
- Cell therapy for brain tumors: The first 60 years.Cell reports. Medicine · 2026Review
- CAR T-cell and oncolytic virus dynamics and determinants of combination therapy success for glioblastoma.Mathematical biosciences · 2025Article
- Mathematical Model of CAR T-Cell Therapy for a B-Cell Lymphoma Lymph Node.Bulletin of mathematical biology · 2025Article
- Special Populations in Ambulatory Surgery: Oncologic, Lactating, Transgender and Gender Diverse, and Suicidal Ideation.International anesthesiology clinics · 2025Article
- Therapeutic advantage of combinatorial chimeric antigen receptor T cell and chemotherapies.Pharmacological reviews · 2025Review
- Mathematical models and computational approaches in CAR-T therapeutics.Frontiers in immunology · 2025Review
- The Kinetics of Inflammation-Related Proteins and Cytokines in Children Undergoing CAR-T Cell Therapy-Are They Biomarkers of Therapy-Related Toxicities?Biomedicines · 2024Article
- Review
- CAR T cells and T cells phenotype and function are impacted by glucocorticoid exposure with different magnitude.Journal of translational medicine · 2024Article
- Patterns of neurotoxicity among patients receiving chimeric antigen receptor T-cell therapy: A single-centre cohort study.European journal of neurology · 2024Article
- Dexamethasone potentiates chimeric antigen receptor T cell persistence and function by enhancing IL-7Rα expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Impact of corticosteroids on the efficacy of CD19/22 CAR-T cell therapy in pediatric patients with B-ALL: a single-center study.Frontiers in pediatrics · 2024Article
- A systems and computational biology perspective on advancing CAR therapy.Seminars in cancer biology · 2023Review
- Dexamethasone and OLT1177 Cooperate in the Reduction of Melanoma Growth by Inhibiting STAT3 Functions.Cells · 2023Article
- Data driven model discovery and interpretation for CAR T-cell killing using sparse identification and latent variables.Frontiers in immunology · 2023Article
- Prospective approaches to enhancing CAR T cell therapy for glioblastoma.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) T-cell therapy is potentially an effective targeted immunotherapy for glioblastoma, yet there is presently little known about the efficacy of CAR T-cell treatment when combined with the widely used anti-inflammatory and immunosuppressant glucocorticoid, dexamethasone. Here we present a mathematical model-based analysis of three patient-derived glioblastoma cell lines treated in vitro with CAR T-cells and dexamethasone. Advanced in vitro experimental cell killing assay technologies allow for highly resolved temporal dynamics of tumor cells treated with CAR T-cells and dexamethasone, making this a valuable model system for studying the rich dynamics of nonlinear biological processes with translational applications. We model the system as a nonautonomous, two-species predator-prey interaction of tumor cells and CAR T-cells, with explicit time-dependence in the clearance rate of dexamethasone. Using time as a bifurcation parameter, we show that (1) dexamethasone destabilizes coexistence equilibria between CAR T-cells and tumor cells in a dose-dependent manner and (2) as dexamethasone is cleared from the system, a stable coexistence equilibrium returns in the form of a Hopf bifurcation. With the model fit to experimental data, we demonstrate that high concentrations of dexamethasone antagonizes CAR T-cell efficacy by exhausting, or reducing the activity of CAR T-cells, and by promoting tumor cell growth. Finally, we identify a critical threshold in the ratio of CAR T-cell death to CAR T-cell proliferation rates that predicts eventual treatment success or failure that may be used to guide the dose and timing of CAR T-cell therapy in the presence of dexamethasone in patients.
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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.