Fig. 1: Model results predict that immune suppression is the dominant escape mechanism.
From: Immunosuppressive niche engineering at the onset of human colorectal cancer
a Maximum size (i.e., number of cells) of each strategy for different values of suppression (S, σ, columns), blockade (B, ϕ, rows), and antigenicity (inset x-axes). Red dots indicate that the population is eliminated by immune predation, highlighting that clones must have some way to avoid immune predation, either by having low antigenicity (Get Lucky) or actively mitigating attack (Get Smart). As population growth was simulated using an epithelial division rate, these results indicate immune escape should be an early event if the clone is to survive increased predation due to the accumulation of neoantigens associated with the mutation. b, c Outcome of competition, where “Co” means neither strategy would go extinct and could co-exist, “N”, indicates either strategy could win, but the one that does must have a larger starting population size, and “X” means that neither population survived immune predation. b Outcomes of competition between Get Lucky (GL) and Get Smart (GS), over a range of suppression values (S, σ), blockade values (B, ϕ), and antigenicities (γ), such that for GL σ = 0, ϕ = 0, and for GS 0 ≤ ϕ ≤ 1, 0 ≤ ϕ ≤ 1. Get Smart wins out over Get Lucky 71% of the time (7778 out of 11025 parameter combinations). c Outcomes of competition between Suppression (S) and Blockade (B), over a range of suppression values (S, σ), blockade values (B, ϕ), and antigenicities (γ), such that for P σ = 0, 0 ≤ ϕ ≤ 1, and for S ϕ = 0, 0 ≤ σ ≤ 1. Out of the 11,025 parameter combinations, Suppression (S) wins the majority of the time, 55% (6047 parameter combinations), with Blockade (B) winning 17% of the time (1862 parameter combinations). Combined, these results highlight that Get Smart almost always wins out over Get Lucky, while Suppression wins against Blockade. This indicates that having an immune escape strategy (Get Smart), particularly immune suppression, significantly increases a clone’s fitness, allowing it to sweep through the population, often by engineering an immunosuppressive niche.
