Dendritic cell plasticity in tumor-conditioned skin: CD14+ cells at the cross-roads of immune activation and suppression

• Main Authors: Rieneke evan de Ven, Jelle Jan Lindenberg, Dinja eOosterhoff, Tanja Denise De Gruijl
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2013-11-01
• Series: Frontiers in Immunology
• Subjects: Dendritic Cells; Macrophages; Skin; Cancer; immune suppression; human DC subsets
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00403/full

Tumors abuse myeloid plasticity to re-direct dendritic cell (DC) differentiation from T cell stimulatory subsets to immune suppressive subsets that can interfere with antitumor immunity. Lined by a dense network of easily accessible DC the skin is a preferred site for the delivery of DC-targeted vaccines. Various groups have recently been focusing on functional aspects of DC subsets in the skin and how these may be affected by tumor-derived suppressive factors. IL-6, Prostaglandin-E2 and IL-10 were identified as factors in cultures of primary human tumors responsible for the inhibited development and activation of skin DC as well as monocyte-derived DC. IL-10 was found to be uniquely able to convert fully developed DC to immature macrophage-like cells with functional M2 characteristics in a physiologically highly relevant skin explant model in which the phenotypic and functional traits of crawl-out DC were studied. Mostly from mouse studies, the JAK2/STAT3 signaling pathway has emerged as a master switch of tumor-induced immune suppression. Our lab has additionally identified p38-MAPK as an important signaling element in human DC suppression, and recently validated it as such in ex vivo cultures of single-cell suspensions from melanoma metastases. Through the identification of molecular mechanisms and signaling events that drive myeloid immune suppression in human tumors, more effective DC-targeted cancer vaccines may be designed.