T cells need to be activated by dendritic cells (DCs) before they will attack a tumor. Sumimoto et al. (page ) now show that a common skin cancer mutation interferes with this pathway, thus helping the tumor to evade the body's immune defenses.
Activating point mutations in the serine-threonine kinase BRAF are found in 66% of all malignant melanomas. The resulting activation of BRAF-ERK-MAPK signaling—the primary pathway involved in growth factor–induced proliferation of melanocytes—immortalizes the cells.
One BRAF mutation (BRAFV600E), according to Sumimoto and colleagues, also prompts human tumor cells to produce vascular endothelial growth factor, interleukin (IL)-6 and IL-10, all of which inhibit the production of proinflammatory cytokines by dendritic cells (DCs).
Disabling DCs, and thereby preventing their activation of tumor-specific T cells, is a popular tumor cell trick. Indeed, activation of the transcription factor STAT3—common among hematopoietic and epithelial cancers—triggers the production of a similar array of DC-inhibiting cytokines. In that model, blocking STAT3 in tumor-bearing mice resulted in T cell attack on the tumor. Whether blocking BRAF will have the same reinvigorating effect on melanoma-specific T cells awaits the development of an animal model.
Interfering with BRAF signaling might enhance immune-activating antitumor therapies, such as DC immunization or T cell immunotherapy, as activation of the cells induced by these approaches might otherwise be blunted by the tumor's suppressive output. 
