PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems
In this 3-D example, each tumor cell secretes an immunostimulatory factor, and its immunogenicity is modeled as proportional to its mutant oncoprotein expression. (See the previous example in Fig 9.) After 14 days, red immune cells perform a biased random walk towards the immunostimulatory factor, test for contact with cells, form adhesions, and attempt to induce apoptosis for cells with greater immunogenicity. The immune cells successfully attack the tumor initially, leading to partial regression; apoptotic cells are cyan. But strong homing towards gradients of the immunostimulatory factor causes immune cells to “pass” some cells at the outer edge, leading to tumor regrowth. Eventually, immune cells leave the necrotic regions and press their attack on the tumor. This highlights the importance of stochasticity in immune cell movement in mixing with the tumor cells for a more successful immune response. A video is available at S8 Video.