Fig. 4
From: Genetic instability as a driver for immune surveillance
Cancer-Immune response attractors driven by instability. In (a–d) we display the nullclines as we increase mutation probability values. Arrows indicate the system flow towards the small and large tumor attractors. Two transitions can be seen. a At low genetic instability levels of 10 −5 mutations per gene per division, such as those common in mutator tumors, only a large cancer attractor coexists with the unstable tumor-free equilibrium left from the graph at c=0. b Beyond μ∗∼1.6×10−5, two new attractors are created, which correspond to a stable microtumor attractor and an unstable twin [30]. c At μ∗=2.0×10−5, the microtumor attractor becomes smaller; until eventually the attractor of uncontrolled tumor growth is eliminated (d) at mutational levels similar to those attained after Mismatch-Repair knockout [40]. In (e) and (f) we summarise the bifurcation diagrams for the possible scenarios as a function of μ and m. For standard immue migration rates (e, black region in f), mutational increases drive the system across the two transitions observed in (a–d) and towards the controlled tumor state. However, by increasing both μ and m through combining Mismatch Repair knockout with adoptive cell therapy, the total cancer clearance state can be accessed