Figure 2.

Drug-Induced Patient Variance as a Method to Stratify Heterogeneous Samples Pin Points a Role for the Th1-Related Pathway

(A) Schematic shows analysis workflow to determine drug-induced variance.

(B–D) Waterfall plots show the change in variance of cytokines, and gene and protein immune cell signatures in the vehicle control versus drug pressure from NanoString (A), flow cytometry (B), cytokine profiling (C), and immunohistochemistry (D). Calculation for variance can be found in the Transparent Methods section. Positive values indicate protein expressions that are more variable from patient to patient under nivolumab pressure compared with the vehicle control, i.e., the drug has the effect of creating high degree of phenotypic heterogeneity across all the patient samples. Negative values indicate those proteins signatures that are less variable across all patient samples under nivolumab pressure compared with the vehicle control, i.e., nivolumab has the effect of normalizing phenotype across patient samples relative to the vehicle.

(E) Schematic shows the clinical study reported in Chen et al. and Riaz et al.

(F) Waterfall plots show the measurable change of Th1 gene transcription signature in data obtained from Chen et al. and Riaz et al.