期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 28, 期 5, 页码 590-598出版社
WILEY
DOI: 10.1111/pcmr.12392
关键词
melanoma; RAC1; PD-L1; anti-PD-1; immune evasion
资金
- National Institutes of Health [F31-CA174331]
- Melanoma Research Foundation
- National Cancer Institute [1P30CA56036]
- NCI Cancer Center Support Grant [CA-16672]
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
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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