For example, in the Hodgkin/Reed–Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL), S1P has been shown to activate phosphatidylinositide 3-kinase (PI3-K) signaling, an effect that is mediated by the increased expression of S1PR1 and the decreased expression of S1PR2 [40]. This evidence concerns the gene S1PR1 and classic Hodgkin lymphoma.