Table 1.

In vitro effects on human tumor cell lines

Cell linesPD-L1 baseline (RT-PCR)T (IC50, nmol/L) CTGGene expression changes by T at 10 nmol/L, 48 h of treatmenta
CtLevelsPD-L1MAPK (DUSP4/6)Apoptosis (PIK3IP1, TP53INP1, BCL2L11)HLA-I (A, B, C)HLA-II (DMA, DPA, DRA)IL8IL1A, IL1B, VEGFA, NTE5TGFA, EREG, AREG
BRAF-mutant melanoma
YUSITc28Low1NDNDND
12R5-1c22High366NDNDND
A37524Moderate2
SK-MEL-2430Very low10
BRAF WT melanoma
SK-MEL-226Low4
HMVII29Low2
CHL-131Very low>500
KRAS-mutant NSCLC
H35823Moderate29b
Calu629Low21b
A54929Low26b

NOTE: Gene expression levels were evaluated by NanoString and/or RT-PCR.

Abbreviations: CTG, CellTiter-Glo assay for cell growth after 3 days of T treatment; ND, not determined.

  • aCells were treated with trametinib (10 nmol/L) alone in all lines or in combination with dabrafenib (300 nmol/L) in 12R5-1 line for 48 hours.

  • bData from RT-PCR only.

  • cExpression increase by trametinib treatment was only detected by RT-PCR, but not NanoString due to below detection range.

  • ↓, designated decrease with ≤0.5-fold of control.

  • ↑, designated increase with ≥2-fold of control.

  • — designated no change, with less than 2-fold of changes vs. control or below the detection range.