Various studies have demonstrated that immunosuppressive mechanisms can be reversed by blocking the effects of mutant BRAF. BRAF inhibitors can downregulate IL-6, IL-10, and VEGF; decrease the recruitment of Tregs and MDSCs; increase recruitment of CTLs; and increase MHC-I and antigen expression. However, there does seem to be a potential increase in the checkpoint molecules PD-1 and PD-L1.
Experiments have also demonstrated that inhibition of BRAF V600E can increase immune infiltration of the tumour and can lead to a measurable increase in the presence of cytotoxic T cells, both CD4+ and CD8+, which are important in different phases of the T-cell response.
When 2 steps in the MAPK signaling are blocked with inhibitors of BRAF combined with inhibitors of MEK, a similar reduction in the immunosuppressive microenvironment of BRAF-mutant melanoma is observed.
Mandalà M, et al. Lab Invest. 2017;97(2):166-175. Copyright © 2016, Springer Nature. Reprinted with permission by Springer Nature.