PI3K/PTEN in plasmacytoid DCs in melanoma

Plasmacytoid dendritic cells (pDCs) are the primary producers of type I interferons in response to pathogens which they recognize via conserved surface receptors. Furthermore, they recruit and influence the actions of further leukocyte subsets. In addition to anti-viral responses, pDCs are implicated in reaction to malignancies. Treatment of cancers of the skin with imiquimod was shown to especially involve pDC activation. In the microenvironment of some solid tumors, pDCs are found to suppress anti-tumor responses. The PI3K/PTEN signaling pathway was shown to have a role in the development and function of certain cells of the immune system. We are interested in the question of whether and how this signaling pathway regulates immune responses to cancers and explore the possibility of targeting this pathway for cancer treatment.

Plasmacytoid dendritic cells (pDCs) are a relevant innate immune cells in immune defence. One of their most important features is the immediate response to viral infections, which gives pDCs the opportunity to orchestrate anti-viral responses of the infected tissue environment. However these processes need to be tightly regulated. In particular in autoimmune diseases or tumor settings pDCs may either contribute to the severity of disease or on the other hand ameliorate the course of disease. Therefore it is vital to understand the intracellular signaling machinery in pDCs and how this is controlled on a cellular level. One of the pathways important in this respect is the PI3K/PTEN signaling pathway. With this project we wanted to shed some light on the role of these relevant signaling molecules in pDC function in particular in melanoma.