ArticleBMC cancer2021
Normal and cancer fibroblasts differentially regulate TWIST1, TOX and cytokine gene expression in cutaneous T-cell lymphoma.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- T-bet: biological functions, molecular mechanisms, and therapeutic applications: a systematic review.Frontiers in immunology · 2026Pooled it
- M2 Macrophage Polarization Characterizes an Immunosuppressive Microenvironment in Extracranial Arteriovenous Malformations.Biomedicines · 2026Article
- Cellular and molecular aberrations generating new immunotherapeutic approaches in mycosis fungoides and Sézary syndrome: a comprehensive review of literature.Frontiers in immunology · 2026Review
- The emerging role of cancer-associated fibroblasts in hematological malignancies: from their influence on tumor progression and drug resistance to novel therapeutic opportunities.Clinical and experimental medicine · 2025Review
- Angiogenesis and lymphangiogenesis in primary cutaneous lymphomas: a narrative review.Clinical and experimental medicine · 2025Review
- Cancer associated fibroblasts in tumors: focusing on solid tumors and hematological malignancies.Frontiers in oncology · 2025Review
- Article
- Review
- TOX Outperforms FOXP3, CD4 and GATA3 in Histopathological Diagnosis of Early Mycosis Fungoides.Turk patoloji dergisi · 2023Article
- TOX Expression in Mycosis Fungoides and Sezary Syndrome.Diagnostics (Basel, Switzerland) · 2022Article
- Stromal Factors as a Target for Immunotherapy in Melanoma and Non-Melanoma Skin Cancers.International journal of molecular sciences · 2022Review
- Cancer Progression Mediated by CAFs Relating to HCC and Identification of Genetic Characteristics Influencing Prognosis.Journal of oncology · 2022Article
- Malignant and Benign T Cells Constituting Cutaneous T-Cell Lymphoma.International journal of molecular sciences · 2021Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMycosis fungoides (MF) is a primary cutaneous T-cell lymphoma (CTCL) that transforms from mature, skin-homing T cells and progresses during the early stages in the skin. The role of the skin microenvironment in MF development is unclear, but recent findings in a variety of cancers have highlighted the role of stromal fibroblasts in promoting or inhibiting tumorigenesis. Stromal fibroblasts are an important part of the cutaneous tumor microenvironment (TME) in MF. Here we describe studies into the interaction of TME-fibroblasts and malignant T cells to gain insight into their role in CTCL.
methodsSkin from normal (n = 3) and MF patients (n = 3) were analyzed for FAPα by immunohistochemistry. MyLa is a CTCL cell line that retains expression of biomarkers TWIST1 and TOX that are frequently detected in CTCL patients. MyLa cells were cultured in the presence or absence of normal or MF skin derived fibroblasts for 5 days, trypsinized to detached MyL a cells, and gene expression analyzed by RT-PCR for MF biomarkers (TWIST1 and TOX), Th1 markers (IFNG, TBX21), Th2 markers (GATA3, IL16), and proliferation marker (MKI67). Purified fibroblasts were assayed for VIM and ACTA2 gene expression. Cellular senescence assay was performed to assess senescence.
resultsMF skin fibroblast showed increased expression of FAP-α with increasing stage compared to normal. Normal fibroblasts co-cultured with MyLa cells suppressed expression of TWIST1 (p < 0.0006), and TOX (p < 0.03), GATA3 (p < 0.02) and IL16 (p < 0.03), and increased expression of IFNG (p < 0.03) and TBX21 (p < 0.03) in MyLa cells. In contrast, MyLa cells cultured with MF fibroblasts retained high expression of TWIST1, TOX and GATA3. MF fibroblasts co-culture with MyLa cells increased expression of IL16 (p < 0.01) and IL4 (p < 0.02), and suppressed IFNG and TBX21 in MyLa cells. Furthermore, expression of MKI67 in MyLa cells was suppressed by normal fibroblasts compared to MF fibroblasts.
conclusionSkin fibroblasts represent important components of the TME in MF. In co-culture model, normal and MF fibroblasts have differential influence on T-cell phenotype in modulating expression of Th1 cytokine and CTCL biomarker genes to reveal distinct roles with implications in MF progression.
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