Multifaceted Kinetics of Immuno-Evasion from Tumor Dormancy

Abstract

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!

The Interplay of Intrinsic and Extrinsic Bounded Noises in Biomolecular Networks

“…A relevant issue that we are going to investigate in the next future is the role of the specific extrinsic bounded perturbations. Indeed, in non-genetic systems affected by bounded noises it has been shown that the effects of the perturbations depend not only on the above general characteristics of the noise, but also on its whole model [40][41][42]76]. In other words the transitions of a system perturbed by a sine-Wiener noise might be quite different from those induced by another bounded perturbation, for example the Cai-Lin noise [77] or the Tsallis noise [43], also when their amplitude and autocorrelation times are equal.…”

Mathematical models of immune-induced cancer dormancy and the emergence of immune evasion

“…Additionally, in the same paper, the role of immunoediting in cancer evasion through mutation to a resistant clone was studied analytically. Effects of both direct cell contact [37,38] and bounded noise [39] have also been investigated. Interestingly, a spatio-temporal model of emerging cancer cell resistance suggests that escape may occur through declining recognition or increasing resistance (or both) [40].…”