Tumor-mediated inhibition of dendritic cell differentiation is mediated by down regulation of protein kinase C beta II expression.

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 betaII is required for dendritic cell differentiation. Here, we describe our finding that tumors mediate both Stat3 activation and PKC betaII 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 betaII down regulation.