High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma
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- 1 November 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 108 (9), 2957-2964
- https://doi.org/10.1182/blood-2006-04-018218
Abstract
Previous studies showed that most cases of ALK+ anaplastic large-cell lymphoma (ALK+ALCL) do not express SHP1, a tyrosine phosphatase and an important negative regulator for cellular signaling pathways such as that of JAK/STAT. To fully assess the biologic significance of loss of SHP1 in ALK+ALCL, we transfected SHP1 plasmids into 2 SHP1-, ALK+ALCL cell lines, Karpas 299 and SU-DHL-1. After 24 hours of transfection, pJAK3 and pSTAT3 were decreased, and these changes correlated with down-regulation of STAT3 downstream targets including cyclin D3, mcl-1, and bcl-2. Expression of SHP1 in these 2 cell lines also resulted in marked decreases in the protein levels of JAK3 and NPM-ALK, and these effects were reversible by proteosome inhibitor MG132. Conversely, when SHP1 expression in SUP-M2 (a SHP1+ ALK+ALCL cell line) was inhibited using siRNA, pSTAT3, pJAK3, JAK3, and NPM-ALK were all up-regulated. Coimmunoprecipitation studies showed that SHP1 was physically associated with JAK3 and NPM-ALK. SHP1 expression in Karpas 299 and SU-DHL-1 led to significant G1 cell cycle arrest but not apoptosis. To conclude, loss of SHP1 contributes to the pathogenesis of ALK+ALCL by 2 mechanisms: (1) it leaves the tyrosine phosphorylation and activation of JAK3/STAT3 unchecked and (2) it decreases proteosome degradation of JAK3 and NPM-ALK.Keywords
This publication has 31 references indexed in Scilit:
- Activated CD4+CD25+ T cells selectively kill B lymphocytesBlood, 2006
- Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphomaBlood, 2006
- Regulatory T Cells in Ovarian Cancer: Biology and Therapeutic PotentialAmerican Journal of Reproductive Immunology, 2005
- Molecular Pathogenesis of Follicular Lymphoma: A Cross Talk of Genetic and Immunologic FactorsJournal of Clinical Oncology, 2005
- Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell levelEuropean Journal of Immunology, 2005
- Outcome in Hodgkin's Lymphoma Can Be Predicted from the Presence of Accompanying Cytotoxic and Regulatory T CellsClinical Cancer Research, 2005
- Predictive value of Follicular Lymphoma International Prognostic Index (FLIPI) in patients with follicular lymphoma at first progressionAnnals of Oncology, 2004
- Follicular Lymphoma International Prognostic IndexBlood, 2004
- Chronic B cell malignancies and bone marrow microenvironmentSeminars in Cancer Biology, 2002
- Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pyloriThe Lancet, 1993