T cells need to be activated by dendritic cells (DCs) before they will attack a tumor. Sumimoto et al. (page 1651) 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...
