CD200 stifles anti-tumor immunity

Nov 16 2007

The prognosis for individuals with metastatic melanoma (MM) is not good. Therapeutic strategies to enhance the immune response have some clinical benefit; however, most patients eventually succumb to progressive disease, in part because their immune cells known as dendritic cells (DCs) fail to sustain an effective antitumor T cell immune response.

New data generated in vitro using human melanoma cell lines and resected tumors by Norman Sharpless and colleagues at the University of North Carolina School of Medicine, Chapel Hill, has identified one mechanism that represses DC function in MM.

Expression of CD200 mRNA and protein was found to be higher in resected human melanomas than in other solid tumors. Further analysis revealed that expression of CD200 was regulated by the N-RAS/B-RAF/MEK/ERK MAP kinase signaling pathway, which is aberrantly activated in approximately 80% of individuals with MM. In vitro analysis indicated the potential functional significance of high levels of CD200 expression - it enabled melanoma cell lines to repress activation of antitumor T cell immune responses by DCs. The authors therefore suggested that targeting the interaction between CD200 and its receptor might provide a new strategy for the treatment of MM.