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Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
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Published on: December 7, 2019

Antioestrogens enhance tumour necrosis factor receptor 2 (TNF-R2) expression and TNF-R2-mediated proliferation in

J Komi1, O Lassila

  • 1Turku Immunology Centre, Department of Medical Microbiology, Turku University, Finland.

Scandinavian Journal of Immunology
|September 22, 1998
PubMed

Insights

Non-steroidal antioestrogens like toremifene and tamoxifen inhibit T cell proliferation but enhance tumor necrosis factor receptor 2 (TNF-R2) expression and function, revealing a novel mechanism of action for these drugs.

Area of Science:

  • Immunology
  • Pharmacology
  • Cell Biology

Background:

  • Non-steroidal antioestrogens, such as tamoxifen and toremifene, are widely used in cancer therapy.
  • Their effects on immune cells, particularly T cells, are not fully understood.
  • Tumor necrosis factor receptor (TNF) family molecules play critical roles in immune responses.

Purpose of the Study:

  • To investigate the impact of toremifene and tamoxifen on T cell proliferation and TNF receptor expression.
  • To elucidate the role of the c-Jun amino terminal kinase (JNK) pathway in mediating these effects.
  • To explore the functional consequences of altered TNF-R2 expression in antioestrogen-treated T cells.

Main Methods:

  • Treatment of peripheral blood T cells with toremifene and tamoxifen.
  • Assessment of mitogen-induced proliferation and cell surface receptor expression.
  • Analysis of the c-Jun amino terminal kinase (JNK) pathway activation using anisomycin and phorbol 12-myristate 13-acetate (PMA).

Main Results:

  • Toremifene and tamoxifen inhibited mitogen-induced T cell proliferation.
  • Antioestrogens increased the surface expression of tumor necrosis factor receptor 2 (TNF-R2) on activated T cells.
  • This up-regulation enhanced TNF-R2-mediated proliferation.
  • Inhibition of JNK activity by anisomycin down-regulated TNF-R2, while toremifene inhibited PMA-induced JNK activity.

Conclusions:

  • Antioestrogens exert novel effects on T cells by up-regulating TNF-R2 expression and enhancing its-mediated proliferation.
  • The JNK pathway is implicated in the regulation of TNF-R2 expression by antioestrogens.
  • Antioestrogens modulate T cell responses through inhibition of protein kinase C (PKC) and influence on signaling pathways like JNK.

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