Fig. 2.

Integrative in silico modeling defines the tumor immune ecosystem (TIES). (A) Cancer cell decision flowchart. (B) Immune cells motility process. C. Cell-cell interactions process. (C) Biologically defined mechanistic rules guiding tumor and immune cell interactions in the 3D agent based in silico model. A fixed starting malignant cell burden and varying proportions of effector or suppressor immune cell infiltrates were inputted into the model and 10 independent simulations resulted in D. Tumor immune evasion (left panel) or immune-mediated tumor elimination (right panel). Different populations of cells in the agent-based model are depicted as follows: red (proliferating tumor cells), tan (quiescent tumor cells), green (effector immune cells) and purple (suppressor immune cells). (E) Representation of the probability of immune-mediated tumor elimination (IMTE) based on individual tumor immune ecosystems (TIES); y-axis: ratio of malignant cell burden/effector immune cell infiltrate (C₀/E₀); x-axis: ratio of effector/suppressor immune cell infiltrate (E₀/S₀). Color coded: Percent of computer simulations that resulted in immune-mediated tumor elimination (IMTE). Red region, TIES characterized by tumor immune evasion; green region, TIES representing immune-mediated tumor elimination.