Effects of mutations and immunogenicity on outcomes of anti-cancer therapies for secondary lesions

TL;DR

This study presents a mathematical model to analyze how mutations and immune interactions influence the success of anti-cancer therapies on secondary metastatic lesions, revealing complex nonlinear effects and potential for long-term disease control.

Contribution

The paper introduces a novel combined mathematical framework using delay differential equations and agent-based modeling to study secondary tumor response to therapies.

Findings

Mutations and immunoediting significantly affect therapy outcomes.

Tumor morphology and composition are influenced by complex nonlinear interactions.

Actions on primary tumors can unexpectedly clear secondary lesions.

Abstract

Cancer development is driven by mutations and selective forces, including the action of the immune system and interspecific competition. When administered to patients, anti-cancer therapies affect the development and dynamics of tumours, possibly with various degrees of resistance due to immunoediting and microenvironment. Tumours are able to express a variety of competing phenotypes with different attributes and thus respond differently to various anti-cancer therapies. In this paper, a mathematical framework incorporating a system of delay differential equations for the immune system activation cycle and an agent-based approach for tumour-immune interaction is presented. The focus is on those metastatic, secondary solid lesions that are still undetected and non-vascularised. By using available experimental data, we analyse the effects of combination therapies on these lesions and investigate the role of mutations on the rates of success of common treatments. Findings show that mutations, growth properties and immunoediting influence therapies' outcomes in nonlinear and complex ways, affecting cancer lesion morphologies, phenotypical compositions and overall proliferation patterns. Cascade effects on final outcomes for secondary lesions are also investigated, showing that actions on primary lesions could sometimes result in unexpected clearances of secondary tumours. This outcome is strongly dependent on the clonal composition of the primary and secondary masses and is shown to allow, in some cases, the control of the disease for years.