Fig. 6
Programmed death receptor 1/programmed death-ligand 1 inhibitor as a potential treatment strategy against tipifarnib-resistant tumors developed from BC159-T#3. a Receptor–ligand interaction between the programmed death receptor 1 (PD-1) and its ligands (PD-L1/PD-L2) of total cells from BC159-T#3. Arrows indicate the direction of interaction (from ligand to receptor) that expresses more than 10% of the ligand genes (left top panel). Pie charts demonstrating the cell composition that express PDCD1/PD-1, CD274/PD-L1, and PDCD1LG2/PD-L2 genes (left top panel). Heatmap of single cells showing the mRNA expression levels of PDCD1/PD-1, CD274/PD-L1, and PDCD1LG2/PD-L2 genes (left bottom panel). 2D-violin plots represent each interaction of PD-1-PDL1 or PD-L2 (right panel). b Representative images for immunohistochemical staining of PD-L1 in BC159-T#3. Expression is specific in tumor cells in the core and stromal border. Scale bar, 100 μm. c Scatter plot representing the average expression of target ligands (x-axis) and the proportion of target receptors in T cells (y-axis). Circle size is proportional to the number of pairing between target ligands and receptors in log2 scale. dCD274/PD-L1 mRNA expression levels are plotted for BC159-T#1, #2, #3, and TCGA-BLCA samples. All samples are colored by molecular subtype. The samples with HRASQ61R mutation are marked in the bottom row of vertical ticks. eCD274/PD-L1 mRNA expression levels according to HRASQ61R mutation. Patients with HRASQ61R mutation in basal squamous subtype show upregulated expression of CD274/PD-L1. Each box shows the median and IQR (interquartile range, 25th to 75th percentiles), whiskers indicate the highest and lowest value within 1.5 times the IQR, and outliers are marked as dots. f Clinical partial response to atezolizumab (a fully humanized, engineered monoclonal antibody of IgG1 isotype against PD-L1) evaluated by CT scan