Document Type

Article

Publication Date

9-1-2015

Comments

This is the peer reviewed version of the following article: Vu, H. L., Rosenbaum, S., Purwin, T. J., Davies, M. A., & Aplin, A. E. (2015). RAC1 P29S regulates PD-L1 expression in melanoma. Pigment Cell and Melanoma Research, 28(5), 590-598, which has been published in final form at DOI: 10.1111/pcmr.12392. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Abstract

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.

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