FIGURE 1.

Model with 5 variables (shown as bolded ovals) and 11 reactions (shown as numbered circles). (1) Growth of tumor cells. (2) Tumor cells are killed by interaction with Active CD8 that is upregulated by helper and downregulated by regulator cells. (3) Active CD8 cells are inactivated on interaction with tumor cells due to the PD1‐PDL1 interaction. (4) Proliferation of active CD8, increased by helpers, and decreased by regulators. (5) Recruitment of active CD8 into tumor microenvironment (TME). (6) Recruitment of CD4 helpers. (7) Recruitment of CD4 regulators. (8) Clearance of active CD8. (9) Clearance of inactive CD8. (10) Clearance of CD4 helpers. (11) Clearance of CD4 regulators. The model equations are outlined in Figure 3 and the detailed explanations of the modeling assumptions are in the Supplementary Section titled “Model Design.” Pembrolizumab is modeled as decreasing inactivation of CD8 (rate of reaction 3), increasing CD8 proliferation (rate of reaction 4), and recruitment (rate of reaction 5). Ipilimumab is modeled as functioning in the lymph node and increasing influx of active CD8 and CD4 helpers into the TME (rates of reactions 5 and 6) and decreasing influx of CD4 regulators (rate of reaction 7)