ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Local IL-21 promotes the therapeutic activity of effector T cells by decreasing regulatory T cells within the tumor microenvironment.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 64 citations in OpenAlex.
- Trial
- IL-15 and IL-21 synergy improves anti-tumor efficacy of iPSC-derived cytotoxic T cells in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Safety and feasibility of blood-derived multiple antigen-specific endogenously derived T cells (MASE-T) for metastatic melanoma.Immuno-oncology technology · 2026Article
- Advancing osteosarcoma treatment: the impact of intratumoral metabolic reprogramming on immunotherapy.Frontiers in immunology · 2026Review
- TCR-engaging scaffolds selectively expand antigen-specific T-cells with a favorable phenotype for adoptive cell therapy.Journal for immunotherapy of cancer · 2023Article
- Engineered murine IL-21-secreting leukemia cells induce granzyme BCancer immunology, immunotherapy : CII · 2023Article
- Implications of IL-21 in solid tumor therapy.Medical oncology (Northwood, London, England) · 2023Review
- Interleukin gene delivery for cancer gene therapy:Iranian journal of basic medical sciences · 2023Review
- Analysis of causes for poor persistence of CAR-T cell therapyFrontiers in immunology · 2023Review
- Tumor microenvironment: barrier or opportunity towards effective cancer therapy.Journal of biomedical science · 2022Review
- The Role of Inflammatory Cytokines in the Pathogenesis of Colorectal Carcinoma-Recent Findings and Review.Biomedicines · 2022Review
- A clinical trial of IL-15 and IL-21 combination therapy for COVID-19 is warranted.Cytokine & growth factor reviews · 2021Article
- Improving Adoptive T Cell Therapy: The Particular Role of T Cell Costimulation, Cytokines, and Post-Transfer Vaccination.Frontiers in immunology · 2016Review
- Regulatory T cells in the immunotherapy of melanoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Review
- Tumor-associated antigen/IL-21-transduced dendritic cell vaccines enhance immunity and inhibit immunosuppressive cells in metastatic melanoma.Gene therapy · 2014Article
- Disruption of CD8+ Treg activity results in expansion of T follicular helper cells and enhanced antitumor immunity.Cancer immunology research · 2014Article
- Gene therapy of ovarian cancer using IL-21-secreting human umbilical cord mesenchymal stem cells in nude mice.Journal of ovarian research · 2014Article
- Recombinant interleukin-21 plus sorafenib for metastatic renal cell carcinoma: a phase 1/2 study.Journal for immunotherapy of cancer · 2014Article
- Innate and adaptive immune cells in the tumor microenvironment.Nature immunology · 2013Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The eradication of tumors by the immune system depends on the generation of antigen-specific T cells which can migrate to sites of tumor growth and maintain their effector functions despite local tumor-derived T-cell inhibitory factors. Interleukin-21 (IL-21) is an IL-2-related cytokine that has shown limited evidence of antitumor activity in murine models and early phase clinical trials. Effect of local IL-21 on T-cell responses within the tumor microenvironment, however, has not been extensively evaluated. Thus, we developed a stably transfected IL-21-secreting B16 melanoma cell line to test the effects of local IL-21 on endogenous and adoptively transferred T-cell responses. Tumors expressing IL-21 exhibited delayed growth in vivo, which was associated with an increase in activated systemic effector and memory CD8(+) T-cell responses. Local IL-21 also enhanced the therapeutic effects of adoptively transferred gp100-specific T cells and was synergistic with IL-2. The effect was also associated with an increased proliferation of local CD8(+) T cells and decreased accumulation of regulatory CD4(+)FOXP3(+) T cells within the tumor microenvironment. These data suggest that local IL-21 enhances endogenous and adoptively transferred T-cell immunity through increased effector CD8(+) T cells and decreased CD4(+) regulatory T cells in the tumor microenvironment.
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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.