Cancer name Non Small Cell Lung Cancer
Cancer Type NSCLC
Immunotherapy type Immunostimulant OR Targeting Therapy
Treatment Mocetinostat
Drugstatus Investigational
Drugbank ID DB11830(DB05651)
Checkpoints NA
Signature Type Protein
Signature PD-L1
Official Symbol CD274
Mode of action AC_D_UP
Description for ‘mode of action’：the ‘mode of action’ for signature is composed of three parts: A_B_C. A describes the level at which the corresponding signature changes, it may contain the following values: TRAN(translation), PROT(protein), CE(cell), METH(methylation), AC(acetylation), PHOS(phosphorylation), MU(mutation), SNP(single nucleotide polymorphism), GLYC(glycosylation) and PATH(pathway). B describes the corresponding signature in which cancer immunotherapy condition group has changed, it may contain the following values: R (immunotherapy response group), NR(immunotherapy non-response group), D (Immunotherapy group), ND (No immunotherapy group). C describes the change detail (specific direction) of the corresponding signature, it may contain the following values: UP (High gene/protein expression or increased cellular abundance or enhanced epigenetic modification), DN (Low gene/protein expression or reduced cellular abundance or attenuated epigenetic modifications), LOSS (deletion mutation), GAIN (gain mutation)，Other. For example, the search/browse detail result for CD274 was “PROT_R_UP”, it can be interpreted that the protein level of CD274 was upregulated in immunotherapy response individuals.
Experimental cell lines
Description PD-L1 expression was consistently upregulated in a concentration-dependent manner in all cell lines tested. To confirm that the increased RNA expression of PD-L1 translated into increased surface protein, we measured surface protein expression by flow cytometry. PD-L1 surface expression was consistently upregulated following 48h mocetinostat treatment across multiple cell lines.Promoter region occupancy of HDAC2 and increased H3K27Ac and H3K4me3 was observed at several mocetinostat target genes following 48 h of 1000 nM mocetinostat treatment including PD-L1, HLA-B, HLA-C and MIC-A/B.
PMID 29124315
Title The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy