Immune Evasion through Competitive Inhibition: the Shielding Effect of non-Stem Cancer Cells
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2014
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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 (Kareva and Hahnfeldt, 2013). This connection comes from
up-regulation 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
investigate using an agent-based model, leading to a prediction that relative
CSC to non-CSC ratio will vary with the strength of the host immune response,
with the highest occurring at an intermediate state of immune activation. 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 allowing CTLs
to most effectively reach and eliminate CSCs.
| Reference Key |
kareva2014immune
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|---|---|
| Authors | Irina Kareva |
| Journal | arXiv |
| Year | 2014 |
| DOI |
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