Hodgkin's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Hodgkin's Disease, including details on causes, cancer, lymphoma, stages, symptoms. | ||||||||
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Prostaglandin E2 impairs CD4+ T cell activation by inhibition of lck: implications in Hodgkin's lymphoma.Chemnitz JM, Driesen J, Classen S, Riley JL, Debey S, Beyer M, Popov A, Zander T, Schultze JL Molecular Tumor Biology and Tumor Immunology, Department of Internal Medicine I, University of Cologne, Joseph-Stelzmann-Strasse 9, 50924 Cologne, Germany. Many tumors, including Hodgkin's lymphoma, are associated with decreased cellular immunity and elevated levels of prostaglandin E(2) (PGE(2)), a known inhibitor of CD4+ T cell activation, suggested to be involved in immune deviation in cancer. To address the molecular mechanisms tumor-derived PGE(2) might have on primary human CD4+ T cells, we used a whole genome-based transcriptional approach and show that PGE(2) severely limited changes of gene expression induced by signaling through the T cell receptor and CD28. This data suggests an interference of PGE(2) at an early step of T cell receptor signaling: indeed, PGE(2) stimulation of T cells leads to inactivation of lck and reduced phosphorylation of ZAP70. Antiapoptotic genes escaped PGE(2)-induced inhibition resulting in partial protection from apoptosis in response to irradiation or Fas-mediated signaling. As a functional consequence, PGE(2)-treated CD4+ T cells are arrested in the cell cycle associated with up-regulation of the cyclin/cyclin-dependent kinase inhibitor p27(kip1). Most importantly, CD4+ T cells in Hodgkin's lymphoma show similar regulation of genes that were altered in vitro by PGE(2) in T cells from healthy individuals. These data strongly suggest that PGE(2) is an important factor leading to CD4+ T cell impairment observed in Hodgkin's lymphoma. Published 20 January 2006 in Cancer Res, 66(2): 1114-22.
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