Figure 2. Nivolumab and ipilimumab differentially impact on peripheral blood immunophenotypes.

(A) The median frequency at baseline on the x axis and the week-13 median frequency on the y axis is shown for significantly changed immunophenotypes (P < 0.05, Wilcoxon signed-rank test) in nivolumab-treated patient samples. Each dot represents an immunophenotype and is colored by P value. The purple dotted line with a slope of 1 corresponds to no change in median frequency. (B) Ipilimumab-treated patient samples are likewise shown. (C) A Venn diagram is shown with the number of significantly changed immunophenotypes in each group and the overlap. The 525 immunophenotypes are those overlapping with changes in the same direction in both NIVO- and IPI-treated patient samples. (D) The median relative change from baseline to week 13 in nivolumab-treated patient samples on the x axis and the relative change in ipilimumab-treated patient samples on the y axis is shown for the 584 overlapping immunophenotypes. The purple dotted lines correspond to no change in median frequency. (E) The delta values (week 13 minus baseline) of the 584 overlapping phenotypes were used in an elastic net regularized regression model to categorize whether a paired patient sample received nivolumab or ipilimumab treatment. The receiver operator characteristic (ROC) and resulting AUC for all paired samples is shown by the dotted black line in the left panel. The ROC and AUC for responding patient samples is shown in blue and for progressing patient samples in red. The model values for nivolumab and ipilimumab-treated paired patient samples are plotted in the right panel. Box plots show median ± quartiles with whiskers indicating range.