Taken as whole, we demonstrate for the first time that i) IL-27 exerts direct anti-proliferative and anti-angiogenic effects on PCa cells expressing IL-27R both in vitro and in pre-clinical models; ii) in humans, IL-27R is expressed in well-differentiated and localized PCa, but not in high grade and advanced stages PCa; iii) in the tumor stroma, immune and endothelial cells express IL-27R. This evidence concerns the gene IL27RA and posterior cortical atrophy.