RAC1 P29S regulates PD‐L1 expression in melanoma

Summary Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC 1 in 5–9% of samples, but the role of RAC 1 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 RAC 1 P29S expression and downregulated with RAC 1 P29S depletion. Using the melanoma patient samples in TCGA , we found PD ‐L1 expression to be significantly increased in RAC 1 P29S patients compared to RAC 1 WT as well as other RAC 1 mutants. The finding that PD ‐L1 is upregulated suggests that oncogenic RAC 1 P29S may promote suppression of the antitumor immune response. This is a new insight into the biological function of RAC 1 P29S mutations with potential clinical implications as PD ‐L1 is a candidate biomarker for increased benefit from treatment with anti‐ PD 1 or anti‐ PD ‐L1 antibodies.