Journal
IMMUNOLOGIC RESEARCH
Volume 46, Issue 1-3, Pages 165-176Publisher
HUMANA PRESS INC
DOI: 10.1007/s12026-009-8118-5
Keywords
Protein kinase C beta II (PKC beta II); Dendritic cell differentiation; Tumor-mediated immune suppression; Myeloid-derived suppressor cell; Stat3
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Tumor-mediated immune suppression occurs through multiple mechanisms, including dysregulation of dendritic cell differentiation. This block in differentiation results in fewer dendritic cells and an accumulation of immunosuppressive myeloid- derived suppressor cells and is thought to contribute to tumor outgrowth and to act as an impediment to successful anti-cancer immunotherapy. Tumor-mediated myeloid dysregulation is known to be Stat3 dependent; however, the molecular mechanism of this Stat3 signaling remains poorly defined. We have previously shown that PKC beta II is required for dendritic cell differentiation. Here, we describe our finding that tumors mediate both Stat3 activation and PKC beta II down regulation in DC progenitor cells, a process mimicked by the expression of a constitutive active Stat3 mutant. This demonstrates that tumor-mediated myeloid dysregulation may be mediated by Stat3- induced PKC beta II down regulation.
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