Enhancement of anti-tumor activity in vitro and in vivo by CD150 and SAP.

Signaling lymphocyte activation molecule (SLAM, CD150) is a co-stimulatory receptor involved in T cell activation. The activity of CD150 is dependent on the intracellular signaling molecule SAP. Here, we investigated anti-CD3 activated human lymphocytes, transfected either with CD150-plasmid or with CD150- or SAP-siRNA in cytotoxicity assays against human colon cancer cells in vitro and in a xenograft model (CB/Scid/CrL mice) in vivo. Up-regulation or silencing of CD150 was accompanied by increased or decreased cytotoxic activity, respectively. Similar effects could also be shown in an IFN-gamma ELISpot assay. Furthermore, CD150 co-localized after activation with lipid rafts in specific membrane compartments on CD8 T cells. Treatment of xenografted mice with CD150 over-expressing lymphocytes decelerated tumor growth significantly. Lymphocytes were detectable in spleen 18 days after injection and expressed mainly CD8, CD45RO and CD150 above average. In conclusion, over-expression of CD150 in lymphocytes is accompanied with enhanced cytotoxic activity and IFN-gamma secretion in vitro and anti-tumor activity in vivo, whereas silencing of CD150 down-regulates effector functions. Adoptive cell transfer of CD150 over-expressing lymphocytes results in an accumulation of CD8, CD45RO and CD150 cells in tumor and spleen indicating together with the observed CD150 co-localization with lipid rafts that CD150 mediates a Th1 response.