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    GENE:

    IL21 (Interleukin 21)

    i
    Other names: IL21, IL-21, Za11, Interleukin-21, Interleukin-21 Isoform, CVID11
    4d
    Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics. (PubMed, Science)
    An IL-10-based Trikine induced immune infiltration into poorly immunogenic tumors, showing efficacy in pre-clinical models of small cell lung cancer and pancreatic cancer. Trikines obviate the need for cell engineering to customize STAT signatures and may hold potential for immunotherapy.
    Journal
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    IL2 (Interleukin 2) • IL10 (Interleukin 10) • IL21 (Interleukin 21)
    10d
    The presence of CD11c+ B cells with potent effector memory phenotype in lung adenocarcinoma correlates with overall patient survival. (PubMed, Cancer Immunol Res)
    Stimulation also induced IL-12, IL-21, and TNF-α secretion, which are cytokines known to enhance antitumor immunity. Overall, the data indicte that CD11c+ TIL-Bs are a potential target for anticancer therapeutic approaches and/or a potential prognostic biomarker for cancer prognosis.
    Journal • IO biomarker
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    CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • CD79A (CD79a Molecule) • CD40 (CD40 Molecule) • IL21 (Interleukin 21) • ITGAX (Integrin Subunit Alpha X)
    18d
    Inflammatory profile associated with hyperglycemia in children with type 1 diabetes. (PubMed, J Diabetes Complications)
    A broad range of inflammatory mediators are correlated with HbA1c in children with T1D. These inflammatory changes precede development of T1D complications, suggesting that possible pathophysiologic involvement should be investigated.
    Journal
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    IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • MMP2 (Matrix metallopeptidase 2) • CCL2 (Chemokine (C-C motif) ligand 2) • IL18 (Interleukin 18) • CCL8 (C-C Motif Chemokine Ligand 8) • IL17A (Interleukin 17A) • IL23A (Interleukin 23 Subunit Alpha) • CCL27 (C-C Motif Chemokine Ligand 27) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • IL13 (Interleukin 13) • IL21 (Interleukin 21) • IL4 (Interleukin 4) • MMP1 (Matrix metallopeptidase 1) • CXCL1 (Chemokine (C-X-C motif) ligand 1) • IL33 (Interleukin 33) • LIF (LIF Interleukin 6 Family Cytokine)
    25d
    IL21-STAT3 controls the pentose phosphate pathway to support metabolic reprogramming and tumor progression in chronic lymphocytic leukemia. (PubMed, Hemasphere)
    In contrast, silencing transketolase (TKT)-the rate-limiting enzyme of the non-oxidative PPP-abolished tumor engraftment in vivo, demonstrating that CLL cells rely on this pathway within the tumor microenvironment. These findings uncover a CLL-specific metabolic reprogramming wherein IL-21-STAT3 drives PPP activity and identify the nonoxidative PPP as a critical in vivo vulnerability of leukemic cells in the murine CLL model.
    Journal
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    STAT3 (Signal Transducer And Activator Of Transcription 3) • IL21 (Interleukin 21)
    27d
    Optimal genetic feeder cell-expanded and engineered NK cell products are composed of CD56bright and CD56dim NK cells. (PubMed, Cancer Immunol Immunother)
    Eventually, sorted and expanded NK cells acquire the same activated phenotype, but can be distinguished by CD16 expression, predominantly maintained by CD56dim cells, resulting in superior antibody-dependent cellular cytotoxicity. Together these findings indicate that preselection of a single subset is redundant, and that bulk isolation enables optimal NK cell engineering by leveraging the complementary strengths of CD56bright and CD56dim NK cells.
    Journal
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    IL21 (Interleukin 21)
    28d
    Frontiers of cytokine engineering in CAR cell therapy for cancer. (PubMed, Front Oncol)
    Furthermore, the review explores synthetic and inducible cytokine circuits that enable spatial and temporal control of cytokine release, improving therapeutic precision and reducing systemic toxicity. Collectively, these innovations represent a paradigm shift toward next-generation, cytokine-engineered CAR therapies with enhanced efficacy, safety, and durability against both hematologic and solid tumors.
    Review • Journal • IO biomarker
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    IL2 (Interleukin 2) • IL10 (Interleukin 10) • IL18 (Interleukin 18) • IL15 (Interleukin 15) • IL21 (Interleukin 21) • IL7 (Interleukin 7)
    28d
    Attenuated Salmonella secreting interleukin-21 activates T-cells and induces anti-tumor effects. (PubMed, Acta Pharm Sin B)
    Tumor-bearing mice treated with the combination therapy with anti-PD-L1 antibodies showed improved survival rates and enhanced tumor growth inhibition. This study demonstrates the tumor-targeting capability and in vivo safety of Salmonella, highlighting its potential as a powerful cancer therapy platform.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • IL21 (Interleukin 21)
    1m
    Safety and feasibility of blood-derived multiple antigen-specific endogenously derived T cells (MASE-T) for metastatic melanoma. (PubMed, Immunooncol Technol)
    In this phase I, first-in-human, clinical trial (NCT04904185), six patients with ICI-resistant MM received MASE-T therapy preceded by 3 days of lymphodepleting chemotherapy with cyclophosphamide and fludarabine phosphate. This trial demonstrates that Ag-scaffold-driven expansion of TAA-specific T cells from the peripheral blood of patients with MM is feasible, and the resulting MASE-T infusion product can be safely administered. However, further development is required to unleash the full potential of this technology.
    Journal • First-in-human
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    IL2 (Interleukin 2) • IL21 (Interleukin 21)
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    cyclophosphamide • fludarabine IV
    2ms
    IL-21 enhances the cytotoxicity of intratumoral CD8+ T cells improving radiation efficacy. (PubMed, JCI Insight)
    Our findings suggest that IL-21 is a promising adjuvant to radiotherapy, potentially improving the treatment efficacy through TME enhancement. This study provides a foundation for future clinical exploration of IL-21 for enhancing radiotherapy.
    Journal
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    CD8 (cluster of differentiation 8) • IL21 (Interleukin 21)
    2ms
    Expression of Type 2 Innate Lymphoid Cell and IL-9 and Other Related Cytokines in Chronic Lymphocytic Leukemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    In CLL patients, the proportions of ILC2 and IL-9 in peripheral blood and lymph nodes increase, and ILC2 and IL-9 show colocalization in lymph nodes. There is a positive correlation between ILC2 and IL-9 in the peripheral blood of CLL patients, the ability of ILC2 to secrete IL-9 is increased, and ILC2 may affect the occurrence and development of CLL through IL-9.
    Journal
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    IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • TGFB1 (Transforming Growth Factor Beta 1) • GATA3 (GATA binding protein 3) • IL21 (Interleukin 21) • PTGDR2 (Prostaglandin D2 Receptor 2)
    2ms
    How Cytokines Regulate Immune Response Toward Chronic Allograft Rejection? (PubMed, Results Probl Cell Differ)
    To induce transplant tolerance, it is necessary to maintain physiological cytokine levels as well as boost the function of T regulatory T (Treg) cells producing IL-10, IL-35, and TGFβ. This chapter emphasizes the necessity of maintaining a balance by cytokines to divert them from the inflammation path producing chronic rejection to normal function support combined with Treg-dominated transplantation tolerance.
    Journal
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    IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • TGFB1 (Transforming Growth Factor Beta 1) • IFNA1 (Interferon Alpha 1) • IL15 (Interleukin 15) • IL21 (Interleukin 21) • IL4 (Interleukin 4) • IL7 (Interleukin 7)
    2ms
    IL-21 promotes the anti-tumor effect of anti-CD47 chimeric antigen receptor macrophages in ovarian cancer. (PubMed, Commun Biol)
    In addition, an IL-21 modification significantly enhanced the tumor microenvironmental regulation of immunosuppression mediated by anti-CD47 CAR-Ms in vivo, thereby improving their therapeutic efficacy in a mouse model of ovarian cancer, without any obvious adverse effects. Taken together, these results suggest that anti-CD47 CAR-Ms combined with IL-21 is a promising treatment strategy for ovarian cancer.
    Journal
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    IL21 (Interleukin 21)