Supplementary Figures and Tables from Hypoxia-Driven Mechanism of Vemurafenib Resistance in Melanoma

Figure S1. Chemical Structure of MSC2156119J (Tepotinib, EMD 1214063); Figure S2. Morphology of melanoma cell 2D ambient air cultures and spheroids; Figure S3. The immunofluorescent staining of DAPI and LOX-1 in A375 2D ambient air cultures; Figure S4. The immunofluorescent staining of LOX-1 in MEL1617 3D spheroids on day 3 and 8 of cultures; Figure S5. The human phospho-kinase antibody array of 451Lu spheroids and 2D ambient air cultures; Figure S6. The human phospho-kinase antibody array of A375 spheroids and 2D ambient air cultures; Figure S7. Effect of PLX4032 on BRAF-ERK pathway in melanoma cells under hypoxic conditions. Supplementary Table S1: Primers for RT-PCR and Real-time PCR; Supplementary Table S2: Patient Characteristics; Supplementary Table S3: List of cutaneous melanoma cell lines in CCLE project</p

Supplementary Figures S1 - S9, Table S1 from The Immune Microenvironment Confers Resistance to MAPK Pathway Inhibitors through Macrophage-Derived TNFα

Supplementary Figures S1 - S9, Table S1. Supplementary Figure S1 (related to Figure 1) shows TNFR expression in melanoma cells. Supplementary Figure S2 (related to Figure 2) shows an NF-κBα binding site in the MITF promoter and MITF target gene expression. Supplementary Figure S3 (related to Figure 3) shows macrophage differentiation and their effect on melanoma cells, keratinocytes and fibroblasts. Supplementary Figure S4 (related to Figure 3) shows M1 and M2 macrophage marker expression in melanoma. Supplementary Figure S5 (related to Figure 4) shows that MEK inhibition does not affect the protective function of macrophages. Supplementary Figure S6 (related to Figure 4) BRAFi and MEKi induced changes in macrophage marker expression in vivo. Supplementary Figure S7 (related to Figure 6) shows that IKK inhibition and MEK inhibition synergise in vitro. Supplementary FigureS8 (related to Figure 6) shows that TNFα protects from BRAF inhibition and IKK and BRAF inhibition synergise in vitro. Supplementary Figure S9 (related to Figure 7) shows the expression of macrophage markers in IKKi treated allografts. Supplementary Table S1 lists patient details.</p

Supplementary Figure Legend from Elucidating Distinct Roles for <i>NF1</i> in Melanomagenesis

PDF file - 78K</p

Supplementary Tables 1 - 3 from Elucidating Distinct Roles for <i>NF1</i> in Melanomagenesis

PDF file - 84K, Supplementary Table 1. NF1 and BRAF mutations identified in human melanoma cell lines. Data were generated in this study when specified and collected from publicly available databases. (CCLE: Cancer Cell Line Encyclopedia, COSMIC: Catalogue of Somatic Mutations in Cancer, WT: wild-type, n/a: not analyzed). Supplementary Table 2. Somatic NF1 mutations detected in human primary melanomas.Supplementary Table 3. NF1 expression is lost in malignant and metastatic melanomas. Quantification of complete NF1 loss of the human melanoma tissue micorarray ME804a (US Biomax Inc)</p

Supplementary Figure 1 from Elucidating Distinct Roles for <i>NF1</i> in Melanomagenesis

PDF file - 96K, Schwann cells (RT4) expressing an inducible RAF construct (∆RAF:ER) were treated with the indicated concentrations of hydroxy-tamoxifen (4-OHT) in the absence and presence of a short hairpin RNA (shRNA) specific for NF1. RAS-GTP levels were assessed using a RAS pulldown assay. Immunoblots on total cell lysates are shown.</p

Supplementary Figure 2 from Elucidating Distinct Roles for <i>NF1</i> in Melanomagenesis

PDF file - 175K, Dose response curves for PLX4720 in BRAFV600E mutant melanoma cell lines (WM3526 (A) and A375 (B)) in the absence or presence of a short hairpin RNA (shRNA) specific for NF1. Cells were treated with PLX4720 at the indicated concentrations, counted and plotted relative to untreated controls.</p

Supplementary Figure Legend from Response to BRAF Inhibition in Melanoma Is Enhanced When Combined with Immune Checkpoint Blockade

Supplementary Figure Legend</p

Supplementary Figures S1-S19 from A Melanoma Cell State Distinction Influences Sensitivity to MAPK Pathway Inhibitors

PDF file 615K, This file contains a series of additional experiments and analyses related to Main Figures 1-5, including more extensive transcript/drug sensitivity correlations, mRNA-expression validation experiments,IHC controls, confirmation of drug sensitivity predictions and perturbation experiments</p

Supplementary Figures from Response to BRAF Inhibition in Melanoma Is Enhanced When Combined with Immune Checkpoint Blockade

Supplementary Figure 1. BP cells behave like classic BRAFV600E melanomas after BRAF inhibition. Supplementary Figure 2. Subcutaneously implanted BP cells develop into tumors. Supplementary Figure 3. BRAF inhibition is associated with an increase in density of tumor-infiltrating T cells. Supplementary Figure 4. Kinetics of functional CD8 T cell markers. Supplementary Figure 5. BRAF inhibition is associated with an increase in overall PD-L1 and PD-L2 expression in the tumor. Supplementary Figure 6. Cell type specific changes in PD-L1 expression after BRAF inhibitors. Supplementary Figure 7. PD-1 or PD-L1 blockade synergy with BRAF inhibitors is associated with increased density of tumor-infiltrating T cells.</p

Supplementary Tables S1-S2 from A Melanoma Cell State Distinction Influences Sensitivity to MAPK Pathway Inhibitors

PDF file 89K, This file contains a table listing the top 75 genes correlated with RAF-inhibitor sensitivity in BRAFV600E-mutant cell lines as well as a table describing the IHC results summarized in Main Figure 2b and 2c</p