HDACs and Tumor Immune Responses

Dysfunction of the immune system is one way for tumor cells to escape attack from immune cells. HDACs may play roles in the regulation of immune system. HDAC inhibition can negatively regulate the functions of dendritic cells, important types of immune cells, by regulating the acetylation of signal transduction and activation of transcription 3 (STAT3), a crucial transcription activator which responds to the stimuli of cytokines, such as interferon, growth factors, and hormones (Sun et al. 2009). STAT3 is implicated in the regulation of immune cells and a variety of autoimmune diseases by regulating immune cell growth and apoptosis (Yang et al. 2007). HDAC1 binding to STAT3 in an interleukin-6 (IL-6)-dependent manner is required for the nucleocytoplasmic distribution of STAT-3, and affects the responsiveness of STAT3 target genes (Ray et al. 2008). A mutant of STAT3 defective in acetylation blocked STAT3-mediated NF-kappaB p100 processing to p52 and also acted as a dominant negative in blocking the production of p52, which could protect cells from apoptosis and facilitate lymphocyte hyperplasia and transformation (Nadiminty et al. 2006).

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