PhysiCell demo: immune cells attacking a heterogeneous tumor
This is Video S8 in Ghaffarizadeh et al. (2018). A higher-resolution (4K) video can be streamed at https://www.youtube.com/watch?v=nJ2urSm4ilU
This is a PhysiCell demo of immune cells (red) attacking a 3-D heterogeneous tumor, using a basic biophysical model of an adaptive immune response to a tumor. In the simulation:
1) Cancer cells each have an individual expression of a mutant oncoprotein, which drives proliferation. Yellow cells divide faster (lots of oncoprotein) than blue ones (very little oncoprotein).
2) If the tumor gets too big, it outstrips the nutrient supply and a necrotic core (dead center) forms.
3) As a simple model, tumor cells release an immunostimulatory factor that diffuses outward. Cells are assumed to have immunogenicity proportional to the mutant oncoprotein (e.g., by altering MHC with mutant peptides).
4) At 14 days, we introduce 7500 immune cells (red) which perform a biased random walk towards the immunostimulatory factor.
5) Whenever an immune cell touches another cell, it:
.. a) adheres to the cell
.. b) checks for immunogenicity
.. c) induces apoptosis in the tumor cell at a rate proportional to immunogenicity)
.. d) detaches either after a random time or after inducing apoptosis in the tumor cell
6) Immune cells break away from newly apoptotic cells (cyan) and continue to seek more targets.
The simulation took about 2 days on a quad-core desktop (i7-4770k), including time spent on saving simulation data once every 3 simulated minutes. Simulations with less frequent output are substantially faster.
Blue cells: tumor cells with oncoprotein < 0.5
Yellow cells: tumor cells with oncoprotein > 1.5
In between: tumor cells with 0.5 < oncoprotein < 1.5
(yellow is greater)
Dark dots: cell nuclei
Cyan cells: apoptotic tumor cells
Brown cells: necrotic tumor cells and debris
Red cells: attacking immune cells.
This work is based on PhysiCell, an open source 3-D modeling package for multicellular biology at http://PhysiCell.MathCancer.org.
Method: Demonstration of PhysiCell, an agent-based, lattice-free model. Cell velocities determined by balance of adhesive, repulsive, and motile forces. Each cell has a phenotypic state governed by stochastic processes derived from nonhomogeneous Poisson processes.