ArticleOncotarget2018
IL-21 modulates memory and exhaustion phenotype of T-cells in a fatty acid oxidation-dependent manner.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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Who cites it
68 citing papers in PubMed, 93 citations in OpenAlex.
- Boosting CAR T cell efficacy in cancer with metabolic insights from design to diet.Nature reviews. Cancer · 2026Review
- C-terminal CD28 phosphorylation, pY218, modulates IL-2 secretion and therapeutic effect of CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Distinct cytokines regulate gene expression and anti-tumor activity in regenerated CD8iScience · 2026Article
- Developing a multimodal therapy for glioblastoma using oncolytic virus delivering CD19 and EGFRvIII antigens and bi-specific CARs.Nature communications · 2026Article
- GITR activation potentiates anti-tumor immunity of tumor-infiltrating lymphocytes expanded from glioblastoma by rescuing exhaustion.Oncogene · 2026Article
- Targeting organelle function in T cells for cancer immunotherapy.Nature reviews. Immunology · 2026Review
- Common gamma chain cytokines-driven optimization of chimeric antigen receptor T cells: Mechanistic insights and future directions.World journal of clinical oncology · 2026Review
- C-terminus CD28 phosphorylation (Y218) modulates IL-2 secretion and antitumor effect of CAR-T cells.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- Impact of IL-21 on CAR T-cell manufacturing: phenotypic, metabolic, and functional outcomes.Frontiers in immunology · 2026Article
- Targeting CAR-T cell exhaustion in non-Hodgkin lymphoma: mechanistic insights and emerging clinical strategies.Frontiers in immunology · 2026Review
- Beneficial effect of resveratrol on T cell oxidative metabolism and anti-tumor function is conditioned by priorMolecular therapy. Methods & clinical development · 2025Article
- Restorative Effects of Synbiotics on Colonic Ultrastructure and Oxidative Stress in Dogs with Chronic Enteropathy.Antioxidants (Basel, Switzerland) · 2025Article
- Optimizing viral transduction in immune cell therapy manufacturing: key process design considerations.Journal of translational medicine · 2025Review
- Chronic IL-21 drives neuroinflammation and promotes lipid accumulation in microglia.Immunity & ageing : I & A · 2025Article
- Adoptive cell therapy for cancer: combination strategies and biomarkers.Frontiers in immunology · 2025Review
- Myeloid cells meet CD8Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Review
- Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD.Cancer cell · 2024Article
- Immunometabolism of CD8Trends in cancer · 2024Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell-based therapies represent a promising strategy for cancer treatment. In this context, cytokines are discussed as a bona fide instrument for fine-tuning T- cell biology. One promising candidate is the pleiotropic interleukin-21 (IL-21) with only little being known regarding its direct effects on human T-cells. Thus, we sought out to characterize the impact of IL-21 on T-cell metabolism, fitness, and differentiation. Culturing T-cells in presence of IL-21 elicited a metabolic skewing away from aerobic glycolysis towards fatty acid oxidation (FAO). These changes of the metabolic framework were paralleled by increased mitochondrial fitness and biogenesis. However, oxidative stress levels were not increased but rather decreased. Furthermore, elevated FAO and mitochondrial biomass together with enhanced antioxidative properties are linked to formation of longer lasting memory responses and less PD-1 expression. We similarly observed an IL-21-triggered induction of central memory-like T-cells and reduced levels of PD-1 on the cell surface. Taken together, IL-21 shifts T-cells towards an immunometabolic phenotype that has been associated with increased survivability and enhanced anti-tumor efficacy. In addition, our data reveals a novel interconnection between fatty acid metabolism and immune function regulated by IL 21.
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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.