Figure 4 from T-Cell Receptor and Immune Gene Expression Pharmacodynamics for Durvalumab Alone and with Tremelimumab or Bevacizumab in Unresectable Hepatocellular Carcinoma

<p>Gene expression. Peripheral blood gene expression changes across the durvalumab plus bevacizumab, durvalumab monotherapy, T75 + D, STRIDE, and tremelimumab monotherapy arms (<b>A</b>) and changes in gene expression signatures in the Hallmark set (<b>B</b>), the consensus tumor microenvironment set (<b>C</b>), and the Bagaev immune set (<b>D</b>) across the durvalumab plus bevacizumab, durvalumab monotherapy, and STRIDE arms. In panel <b>A</b>, to identify differential gene expression in each trial arm, the DESeq2 capability was applied in R to compare the end of cycle 1 with day 1, while adjusting for baseline participant effects. A Venn diagram comparing differential gene expression per trial arm was produced according to the following criteria: |log₂ fold change| ≥ 0.4 and <i>P</i> ≤ 0.05 (<i>P</i> values are unadjusted; no multiple hypothesis testing applied at this stage). In panels <b>B–D</b>, a mixed effects model accounting for random patient effects was applied to the cycle 1 vs. baseline change in signature expression, calculated independently per arm. The values shown in the legends of panels <b>B–D</b> are the estimated slope of the linear regression, comparing the end of cycle 1 with the baseline for each gene expression signature tested. The resulting <i>P</i> values of the test were used to select the signatures illustrated in the heatmap. *, <i>P</i> ≤ 0.05. D, durvalumab monotherapy; T, tremelimumab monotherapy; Treg, regulatory T cell.</p>