Multifaceted kinetics of immuno-evasion from tumor dormancy

Tumor progression is subject to modulation by the immune system. The immune system can eliminate tumors or keep them at a dormant equilibrium size, while some tumors escape immunomodulation and advance to malignancy. Herein, we discuss some aspects of immune evasion of dormant tumors from a theoretical biophysics point of view that can be modeled mathematically. We go on to analyze the mathematical system on multiple timescales. First, we consider a long timescale where tumor evasion is likely due to adaptive (and somewhat deterministic) immuno-editing. Then, we consider the temporal mesoscale and hypothesize that extrinsic noise could be a major factor in induction of immuno-evasion. Implications of immuno-evasive mechanisms for the outcome of immunotherapies are also discussed. In addition, we discuss the ideas that population level tumor dormancy may not be a quiescence phenomenon and that dormant tumors can, at least if modulated by the immune system, live a very active and noisy life!