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RAC 1 P29S regulates PD ‐L1 expression in melanoma
Author(s) -
Vu Ha Linh,
Rosenbaum Sheera,
Purwin Timothy J.,
Davies Michael A.,
Aplin Andrew E.
Publication year - 2015
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12392
Subject(s) - melanoma , cancer research , downregulation and upregulation , pd l1 , exome sequencing , mutation , biology , immune checkpoint , rac1 , mutant , microbiology and biotechnology , immune system , signal transduction , gene , genetics , immunotherapy
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.