Immune evasion through competitive inhibition: The shielding effect of cancer non-stem cells

Authored by Irina Kareva

Date Published: 2015

DOI: 10.1016/j.jtbi.2014.08.035

Sponsors: United States National Institutes of Health (NIH) United States Department of Energy (DOE)

Platforms: NetLogo

Model Documentation: Other Narrative

Model Code URLs: Model code not found

Abstract

It has been recently proposed that the two emerging hallmarks of cancer, namely altered glucose metabolism and immune evasion, may in fact be fundamentally linked. This connection comes from upregulation of glycolysis by tumor cells, which can lead to active competition for resources in the tumor microenvironment between tumor and immune cells. Here it is further proposed that cancer stem cells (CSCs) can circumvent the anti-tumor immune response by creating a ``protective shield{''} of non-stem cancer cells around them. This shield can protect the CSCs both by creating a physical barrier between them and cytotoxic lymphocytes (CTLs), and by promoting competition for the common resources, such as glucose, between non-stem cancer cells and CTLs. The implications of this hypothesis are investigated using an agent-based model, leading to a prediction that relative CSC to non-CSC ratio will vary depending on the strength of the host immune response. A discussion of possible therapeutic approaches concludes the paper, suggesting that a chemotherapeutic regimen consisting of regular pulsed doses, i.e., metronomic chemotherapy, would yield the best clinical outcome by removing the ``protective shield{''} and thus allowing CTLs to most effectively reach and eliminate CSCs. (C) 2014 Elsevier Ltd. All rights reserved.

Tags

Model Evolutionary game-theory Human tumor dormancy Clonal evolution Radiation-resistance Angiogenic switch Initiating cells Innate immunity T-lymphocytes Bone-marrow