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Updated: Sep 20, 2026

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
A tumour necrosis factor alpha autocrine loop contributes to proliferation and nuclear factor-kappaB activation of
Julien Guergnon1, Marie Chaussepied, Paul Sopp
1Laboratoire de Signalisation Immunoparasitaire, URA CNRS 1960, Département de Parasitologie, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
Abstract:
Theileria infection of bovine leucocytes induces uncontrolled proliferation and a transformed phenotype comparable to tumour cells. Infected cells have many characteristics of activated leucocytes and use autocrine loops to augment proliferation. We have shown previously that, in infected B cells, PI3-K controls a granulocyte-macrophage colony-stimulating factor (GM-CSF) autocrine loop to increase both proliferation and activation of the activator protein 1 (AP-1) transcription factor. We show here that the same infected B cells also use a tumour necrosis factor (TNF) alpha autocrine loop that again contributes to proliferation and augments nuclear factor (NF)-kappaB activation. Interestingly, both pharmacological inhibition of TNF synthesis and neutralizing anti-TNF antibodies lead to a reduction in proliferation and a 50% drop in NF-kappaB activation, without inducing apoptosis.
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