ArticleJournal of translational medicine2013
IL-21 promotes the expansion of CD27+ CD28+ tumor infiltrating lymphocytes with high cytotoxic potential and low collateral expansion of regulatory T cells.
Article in Journal of translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 89 citations in OpenAlex.
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- Tumor-infiltrating T Lymphocytes Recognize Thyroid-specific Proteins and Neo-antigens in Follicular Cell-derived Thyroid Cancers.The Journal of clinical endocrinology and metabolism · 2026Article
- From Immunobiology to Clinical Application: Tumor-Infiltrating Lymphocytes in Melanoma.Journal of personalized medicine · 2026Review
- Common gamma chain cytokines-driven optimization of chimeric antigen receptor T cells: Mechanistic insights and future directions.World journal of clinical oncology · 2026Review
- The Pleiotropic Roles of Cytokines in Chimeric Antigen Receptor T-cell Therapy.Cancer immunology research · 2026Review
- Impact of IL-21 on CAR T-cell manufacturing: phenotypic, metabolic, and functional outcomes.Frontiers in immunology · 2026Article
- Generation of functional canine TIL products for solid tumors.Frontiers in immunology · 2026Article
- Tumor-infiltrating lymphocyte expansion protocols for adoptive cell therapy in cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Enhanced anti-tumor efficacy of tumor-infiltrating lymphocytes by GITR agonist in ovarian cancer.Frontiers in immunology · 2025Article
- Mechanism and application of immune interventions in intracerebral haemorrhage.Expert reviews in molecular medicine · 2024Review
- Artificial antigen-presenting cells: the booster for the obtaining of functional adoptive cells.Cellular and molecular life sciences : CMLS · 2024Review
- A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells (TCR-T cells) against hepatocellular carcinoma.Signal transduction and targeted therapy · 2024Article
- Therapeutic potential of interleukin-21 in cancer.Frontiers in immunology · 2024Review
- Unlocking the potential of iPSC-derived immune cells: engineering iNK and iT cells for cutting-edge immunotherapy.Frontiers in immunology · 2024Review
- The Role of CD4 T Cell Help in CD8 T Cell Differentiation and Function During Chronic Infection and Cancer.Immune network · 2023Review
- Expansion of KRAS hotspot mutations reactive T cells from human pancreatic tumors using autologous T cells as the antigen-presenting cells.Cancer immunology, immunotherapy : CII · 2023Article
- Reprogramming the tumor microenvironment by genome editing for precision cancer therapy.Molecular cancer · 2022Review
- Article
- Switch receptor T3/28 improves long-term persistence and antitumor efficacy of CAR-T cells.Journal for immunotherapy of cancer · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundAdoptive cell transfer of tumor infiltrating lymphocytes has shown clinical efficacy in the treatment of melanoma and is now also being explored in other tumor types. Generation of sufficient numbers of effector T cells requires extensive ex vivo expansion, often at the cost of T cell differentiation and potency. For the past 20 years, IL-2 has been the key cytokine applied in the expansion of TIL for ACT. However, the use of IL-2 has also led to collateral expansion of regulatory T cells (Tregs) and progressive T cell differentiation, factors known to limit in vivo persistence and activity of transferred TIL. The use of alternative T cell growth factors is therefore warranted. Here, we have compared the effects of IL-2, -15 and -21 cytokines on the expansion and activation of TIL from single-cell suspensions of non-small cell lung cancer, ovarian cancer and melanoma.
methodsWe applied the K562-based artificial APC (aAPC) platform for the direct and rapid expansion of tumor infiltrating lymphocytes isolated from primary cancer specimens. These aAPC were engineered to express the Fc-γ receptor CD32 (for anti-CD3 antibody binding), the co-stimulatory molecule 4-1BBL, and to secrete either IL-2, IL-15 or IL-21 cytokine.
resultsAlthough IL-2 aAPC induced the greatest overall TIL expansion, IL-21 aAPC induced superior expansion of CD8+ T cells with a CD27+ CD28+ "young" phenotype and superior functional cytotoxic effector characteristics, without collateral expansion of Tregs.
conclusionOur data rationalize the clinical application of IL-21-secreting aAPC as a standardized cell-based platform in the expansion of "young" effector TIL for ACT.
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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.