Figure 4.

Gene signatures in HNSCC patients from the discovery group with their response to immune checkpoint inhibitors. (A) Heatmap representing the down- and upregulated genes involved in antitumor immune activity by unsupervised hierarchical clustering. Scores are scaled to have a mean of zero and a standard deviation of one. The standardized signature scores are truncated at ±3 standard deviations (99% of the data should fall within ±3 standard deviations of the mean). (B) Box plot indicating a significantly lower CTLA-4 signature in patients with a response to ICI as assessed by univariate analysis (p = 0.02). (C) Volcano plot of all gene signatures displays no significant difference between the ICI responders and non-responders in a multivariate analysis. Up indicates upregulated and down indicates downregulated genes. (D) Survival volcano plot of all gene signatures displays no significant difference between the signature’s hazard ratios in a multivariate analysis. Signatures further to the right are associated with a decreased risk of an event relative to the baseline. (E) Box plot indicating a significantly higher IFN downstream signature in patients whose tumors showed a CPS ≥ 1 for PD-L1 immunohistochemistry as assessed by univariate analysis (p = 0.04). (F) Spaghetti plot displaying a decrease in antitumor immune activity from initial diagnosis to r/m disease with start of ICI until the time point of progression under ICI in non-responders, and (G) an increase in CTLA-4 in recurrent tumor material from a patient who initially had a partial response to ICI. * p < 0.05. CPS—combined positive score; Pre-ICI—sample taken just before the start of ICI; Post-ICI—sample taken just after progression under ICI.