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- Title
IL-6, but not IFN-γ, triggers apoptosis and inhibits in vivo growth of human malignant T cells on STAT3 silencing.
- Authors
Regis, G.; Icardi, L.; Conti, L.; Chiarle, R.; Piva, R.; Giovarelli, M.; Poli, V.; Novelli, F.
- Abstract
STAT1 and STAT3 are the main mediators of the signaling of interferons (IFNs) and of gp130 cytokines, respectively. Neoplastic T lymphocytes frequently become resistant to the IFN-γ/STAT1 apoptotic pathway, often because of the downregulation of the IFN-γR2 receptor chain. Many studies suggest that cross-regulation between different STATs, in particular between STAT1 and STAT3, may profoundly affect cytokine/growth factor signaling. Here, the function of STAT3 in the negative regulation of STAT1 apoptotic pathway was investigated by RNA interference-mediated STAT3 silencing in human malignant T lymphocytes. In STAT3-depleted cells, interleukin (IL)-6 acquired the capacity to induce apoptosis, correlating with prolonged STAT1 activation and the induction of major histocompatibility complex (MHC) class I expression. In contrast, in the absence of STAT3, IFN-γ could slightly enhance apoptosis but its ability to induce MHC class I expression was unchanged. Accordingly, IL-6, but not IFN-γ, could significantly impair the in vivo growth of STAT3-depleted human neoplastic T lymphocytes transplanted into severe combined immunodeficient mice. Therefore, treatment with IL-6 and simultaneous STAT3 silencing may represent a potential therapeutic approach to control the expansion of IFN-γ-unresponsive neoplastic T cells.
- Subjects
APOPTOSIS; T cells; LYMPHOCYTES; MAJOR histocompatibility complex; IMMUNOREGULATION
- Publication
Leukemia (08876924), 2009, Vol 23, Issue 11, p2102
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/leu.2009.139