ArticleJournal of leukocyte biology2017
Frontline Science: Functionally impaired geriatric CAR-T cells rescued by increased α5β1 integrin expression.
Article in Journal of leukocyte biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Long-term response to autologous anti-CD19 chimeric antigen receptor T cells in relapsed or refractory B cell acute lymphoblastic leukemia: a systematic review and meta-analysis.Cancer gene therapy · 2023Pooled it
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Biomarker-empowered precision navigation of CAR-T cell therapy.Molecular cancer · 2026Review
- Are we there yet? The road to faster and more efficient CAR T cell manufacturing.Journal of biological engineering · 2026Review
- Chimeric antigen receptor T-cell therapy in patients with malignant glioma-From neuroimmunology to clinical trial design considerations.Neuro-oncology · 2025Review
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Impact of T cell characteristics on CAR-T cell therapy in hematological malignancies.Blood cancer journal · 2024Review
- Article
- Negative Influence of Aging on Differentiation and Proliferation of CD8Veterinary sciences · 2023Article
- Article
- The Interplay between Integrins and Immune Cells as a Regulator in Cancer Immunology.International journal of molecular sciences · 2023Review
- Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells.Blood advances · 2023Article
- Two Ways of Targeting a CD19 Positive Relapse of Acute Lymphoblastic Leukaemia after Anti-CD19 CAR-T Cells.Biomedicines · 2023Article
- Predictive short/long-term efficacy biomarkers and resistance mechanisms of CD19-directed CAR-T immunotherapy in relapsed/refractory B-cell lymphomas.Frontiers in immunology · 2023Review
- Efficacy and safety of CD19 CAR-T cell therapy for acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation.International journal of hematology · 2022Review
- Resistance against anti-CD19 and anti-BCMA CAR T cells: Recent advances and coping strategies.Translational oncology · 2022Review
- Knowns and Unknowns about CAR-T Cell Dysfunction.Cancers · 2022Review
- Regional Delivery of Anti-PD-1 Agent for Colorectal Liver Metastases Improves Therapeutic Index and Anti-Tumor Activity.Vaccines · 2021Article
- ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors.BMC cancer · 2021Article
- Review
Corrections and comments
- Commented on by
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor expressing T cells (CAR-T) are a promising form of immunotherapy, but the influence of age-related immune changes on CAR-T production remains poorly understood. We showed that CAR-T cells from geriatric donors (gCAR-T) are functionally impaired relative to CAR-T from younger donors (yCAR-T). Higher transduction efficiencies and improved cell expansion were observed in yCAR-T cells compared with gCAR-T. yCAR-T demonstrated significantly increased levels of proliferation and signaling activation of phosphorylated (p)Erk, pAkt, pStat3, and pStat5. Furthermore, yCAR-T contained higher proportions of CD4 and CD8 effector memory (EM) cells, which are known to have enhanced cytolytic capabilities. Accordingly, yCAR-T demonstrated higher levels of tumor antigen-specific cytotoxicity compared with gCAR-T. Enhanced tumor killing by yCAR-T correlated with increased levels of perforin and granzyme B. yCAR-T had increased α5β1 integrin expression, a known mediator of retroviral transduction. We found that treatment with M-CSF or TGF-β1 rescued the impaired transduction efficiency of the gCAR-T by increasing the α5β1 integrin expression. Neutralization of α5β1 confirmed that this integrin was indispensable for CAR expression. Our study suggests that the increase of α5β1 integrin expression levels enhances CAR expression and thereby improves tumor killing by gCAR-T.
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.