Fig. 1: Hybrid model of immune-cancer interactions and angiogenesis dynamic.

Schematic representation of the model compartments (a) and the main interactions of immune cells, cancer cells, cytokines, angiogenesis, anti-angiogenic treatment, and oxygen (b). a The compartments of the model and the immune cells and cytokines that are circulated through the entire mouse body. The mouse was divided into the following compartments: the tumor, upper trunk, lower trunk, lymph circulation, and blood circulation. The tumor is modeled as a 3D compartment with a spherical geometry, and the rest of the mouse (upper trunk, lower trunk, blood, and lymph circulation) are modeled as homogenous (0D) compartments. All the compartments are connected with blood and lymph circulation and the balance of all variables was kept through all compartments. Dendritic cells, antigen-presenting cells, CD8⁺ effector T-cells, and cytokines (immunosuppressive and pro-inflammatory) can enter the tumor via the tumor vessels and return back to circulation via the tumor-draining lymphatic vessels. The dendritic cells that are activated to present the tumor antigen can be transported to the lymph node and activate naïve T-cells against the tumor antigen. b The oxygen (O₂) as a nutrient is supplied by the blood vessels and fuels the cancer cells proliferation. Hypoxia induces the VEGF production which attracts the nearby vessels to move through the VEGF gradient. Cancer cells induce immunosuppressive cytokines which can induce immune cell exhaustion which can be inhibited by pro-inflammatory cytokines. CD8⁺ effector T-cells can induce cytolysis in the cancer cells, and dendritic cells (DC) and antigen-presenting cells (APC) can phagocytosis the cancer cells. The antigen-presenting cells activate the naïve T-cells like CD8⁺ T-cells against tumor antigen (CD8⁺ effector T-cells). CD8⁺ effector T-cells and APC produce pro-inflammatory cytokines. Further details are provided in the Supplementary Information. Created with BioRender.com.