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Supplementary Table 1 from Prostaglandin E2 Impairs CD4+ T Cell Activation by Inhibition of lck: Implications in Hodgkin's Lymphoma

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posted on 2023-03-30, 17:03 authored by Jens M. Chemnitz, Julia Driesen, Sabine Classen, James L. Riley, Svenja Debey, Marc Beyer, Alexey Popov, Thomas Zander, Joachim L. Schultze
Supplementary Table 1 from Prostaglandin E2 Impairs CD4+ T Cell Activation by Inhibition of lck: Implications in Hodgkin's Lymphoma

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ARTICLE ABSTRACT

Many tumors, including Hodgkin's lymphoma, are associated with decreased cellular immunity and elevated levels of prostaglandin E2 (PGE2), a known inhibitor of CD4+ T cell activation, suggested to be involved in immune deviation in cancer. To address the molecular mechanisms tumor-derived PGE2 might have on primary human CD4+ T cells, we used a whole genome-based transcriptional approach and show that PGE2 severely limited changes of gene expression induced by signaling through the T cell receptor and CD28. This data suggests an interference of PGE2 at an early step of T cell receptor signaling: indeed, PGE2 stimulation of T cells leads to inactivation of lck and reduced phosphorylation of ZAP70. Antiapoptotic genes escaped PGE2-induced inhibition resulting in partial protection from apoptosis in response to irradiation or Fas-mediated signaling. As a functional consequence, PGE2-treated CD4+ T cells are arrested in the cell cycle associated with up-regulation of the cyclin/cyclin-dependent kinase inhibitor p27kip1. Most importantly, CD4+ T cells in Hodgkin's lymphoma show similar regulation of genes that were altered in vitro by PGE2 in T cells from healthy individuals. These data strongly suggest that PGE2 is an important factor leading to CD4+ T cell impairment observed in Hodgkin's lymphoma. (Cancer Res 2006; 66(2): 1114-22)

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