CD200 mRNA, and the protein it expresses, may be one mechanism that causes dendritic cells (DCs) to fail in sustaining an effective antitumor T-cell immune response in metastatic melanoma (MM), according to researchers at the University of North Carolina School of Medicine.
The investigators found that expression of CD200 mRNA and protein was found to be higher in resected human melanomas than in other solid tumors, and CD200 mRNA expression correlated with disease [progression. 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. “Melanoma cell lines expressing endogenous CD200 repressed primary T-cell activation by DCs, while knockdown of CD200 by shRNA abrogated this immunosuppressive effect,” wrote the scientific team.
The research was published online November 15 in the Journal of Clinical Investigation.