Mechanisms and functional significance of tumour-induced dendritic-cell defects

Abstract

Dendritic cells (DCs) are crucial for the induction of a potent immune response. The dysfunction of DCs in cancer is caused mainly by abnormalities in their differentiation. These abnormalities include decreased production of mature DCs, accumulation of immature DCs and accumulation of immature myeloid cells. Tumour cells produce several factors that affect DC differentiation. These factors include vascular endothelial growth factor, interleukin-10 (IL-10), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-6 and M-CSF. These factors might converge on a common signal-transduction pathway — the JAK2 (Janus activated kinase 2)–STAT3 (signal transducer and activator of transcription 3) pathway. Hyperactivation of STAT3 in haematopoietic progenitor cells results in the accumulation of immature myeloid cells that cannot differentiate into DCs. STAT3 might exert its effect on DC differentiation by inhibiting activation of nuclear factor-κB.