Bistability and Noise-Induced Evasion in Tumor-Immune Dynamics with Antigen Accumulation and Immune Escape
Abstract
Tumor-immune interactions are shaped by both antigenic heterogeneity and stochastic perturbations in the tumor microenvironment, yet the mathematical mechanisms underlying immune phase transitions remain poorly understood. We propose a four-compartment dynamical model that incorporates antigen accumulation and immune escape mutations. Bifurcation analysis reveals bistability between immune surveillance and immune escape states, providing a mechanistic explanation for heterogeneous immune outcomes during tumor progression. In the multistable regime, the stable manifold of a saddle point partitions the state space into distinct basins of attraction, determining the long-term fate of the system. We further analyze how stochastic fluctuations in the tumor microenvironment perturb these separatrices, potentially triggering irreversible state transitions. By characterizing the critical noise intensity and estimating the tipping time, we establish a mathematical framework for assessing noise-induced transitions. The model further predicts that increasing tumor cell death can improve system resilience to stochastic perturbations, whereas stronger immune pressure may facilitate immune escape-highlighting the nonlinear and non-monotonic nature of tumor-immune dynamics.