ArticleCancer discovery2016
Mechanism, Consequences, and Therapeutic Targeting of Abnormal IL15 Signaling in Cutaneous T-cell Lymphoma.
Article in Cancer discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 90 citations in OpenAlex.
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- IL-15 Superagonist SHR-1501 Enhances Immune Responses in Lung Cancer by Modulating Tumor Microenvironment.The clinical respiratory journal · 2025Article
- Models for T-large granular lymphocytic leukemia: how to mimic the cellular interplays in malignant autoimmunity.Leukemia · 2025Review
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- Tethered IL15-IL15Rα augments antitumor activity of CD19 CAR-T cells but displays long-term toxicity in an immunocompetent lymphoma mouse model.Journal for immunotherapy of cancer · 2024Article
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- "Next top" mouse models advancing CTCL research.Frontiers in cell and developmental biology · 2024Review
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- Differential Response of Mycosis Fungoides Cells to Vorinostat.International journal of molecular sciences · 2023Article
- Phenotypic plasticity of malignant T cells in blood and skin of a Sézary syndrome patient revealed by single cell transcriptomics.Frontiers in oncology · 2023Article
- Junction of the redox dynamic, orchestra of signaling, and altered metabolism in regulation of T- cell lymphoma.Frontiers in oncology · 2023Review
- The role of interleukin-15 in the development and treatment of hematological malignancies.Frontiers in immunology · 2023Review
- Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells.Nature biomedical engineering · 2023Article
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- Role of Histone Deacetylases in T-Cell Development and Function.International journal of molecular sciences · 2022Review
- Sézary syndrome patient-derived models allow drug selection for personalized therapy.Blood advances · 2022Article
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Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
unlabelledCutaneous T-cell lymphoma (CTCL) is the most common type of primary cutaneous lymphoma. Here, we report that patients with CTCL show increased IL15 in a clinical stage-dependent manner. Mechanistically, we show that ZEB1 is a transcriptional repressor of IL15 in T cells and that hypermethylation of the ZEB1 binding region within the IL15 promoter, as seen in patients with CTCL, prevents ZEB1 binding and causes increased transcription of IL15 Using a transgenic mouse model of IL15, we provide evidence that overexpression of IL15 induces a spontaneous CTCL that mimics the human neoplasm. Excessive autocrine production of IL15 in T cells inhibits an HDAC1-mediated negative autoregulatory loop, resulting in the upregulation of HDAC1 and HDAC6 and transcriptional induction of the onco-miR-21. Interruption of IL15 downstream signaling with isotype-specific HDAC inhibitors halts (HDAC1) or significantly delays (HDAC6) the progression of CTCL in vivo and provides preclinical evidence supporting a hierarchical model of oncogenic signaling in CTCL. SIGNIFICANCE: To date, CTCL pathogenesis remains unknown, and there are no curative therapies. Our findings not only demonstrate a critical role for IL15-mediated inflammation in cutaneous T-cell lymphomagenesis, but also uncover a new oncogenic regulatory loop in CTCL involving IL15, HDAC1, HDAC6, and miR-21 that shows differential sensitivity to isotype-specific HDAC inhibitors. Cancer Discov; 6(9); 986-1005. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.
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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.