RAC1 P29S regulates PD L1 expression in melanoma
Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC1 in 5 9% of samples, but the role of RAC1 P29 mutations in melanoma biology remains unclear. Using reverse phase protein array analysis to examine the changes in protein/phospho protein expression, we identified cyclin B1, PD L1, Ets 1, and Syk as being selectively upregulated with RAC1 P29S expression and downregulated with RAC1 P29S depletion. Using the melanoma patient samples in TCGA, we found PD L1 expression to be significantly increased in RAC1 P29S patients compared to RAC1 WT as well as other RAC1 mutants. The finding that PD L1 is upregulated suggests that oncogenic RAC1 P29S may promote suppression of the antitumor immune response. This is a new insight into the biological function of RAC1 P29S mutations with potential clinical implications as PD L1 is a candidate biomarker for increased benefit from treatment with anti PD1 or anti PD L1 antibodies.
Pigment cell melanoma research