Abstract
BackgroundThe role of the immune system in tumor progression has been a subject for discussion for many decades. Numerous studies suggest that a low immune response might be beneficial, if not necessary, for tumor growth, and only a strong immune response can counter tumor growth and thus inhibit progression.MethodsWe implement a cellular automaton model previously described that captures the dynamical interactions between the cancer stem and non-stem cell populations of a tumor through a process of self-metastasis. By overlaying on this model the diffusion of immune reactants into the tumor from a peripheral source to target cells, we simulate the process of immune-system-induced cell kill on tumor progression.ResultsA low cytotoxic immune reaction continuously kills cancer cells and, although at a low rate, thereby causes the liberation of space-constrained cancer stem cells to drive self-metastatic progression and continued tumor growth. With increasing immune system strength, however, tumor growth peaks, and then eventually falls below the intrinsic tumor sizes observed without an immune response. With this increasing immune response the number and proportion of cancer stem cells monotonically increases, implicating an additional unexpected consequence, that of cancer stem cell selection, to the immune response.ConclusionsCancer stem cells and immune cytotoxicity alone are sufficient to explain the three-step “immunoediting” concept – the modulation of tumor growth through inhibition, selection and promotion.
Highlights
The role of the immune system in tumor progression has been a subject for discussion for many decades
Complete activation of the adaptive immune system might result in complete tumor eradication, but tumor progression and clinical manifestation has demonstrated the ability of tumor cells to escape immunosurveillance, despite efficient immune responses
A massive influx of activated infiltrating immune cells is correlated with a poor patient prognosis, fueling the hypothesis that an immune reaction may under some circumstances be tumor-promoting [1]
Summary
The role of the immune system in tumor progression has been a subject for discussion for many decades. More recently it has been hypothesized that the immune system can keep the tumor in a somewhat dormant state, but over time select for more aggressive variants with reduced immunogenicity [3] This process, often referred to as immunoediting or tumor sculpting, may occur continuously and has major effects early in tumor progression [4]. Recent evidence has emerged that cancer stem cells can selectively escape the cytotoxic action of immune system killer cells and become enriched during an immune response [7] This raises the prospect that the efficiency of the immune system in eradicating the tumor could be dependent on the ratio of immune reactants to tumor cells. Supporting this idea, a low immune reaction has been shown to accelerate tumor growth, whereas a large numbers of immune reactants inhibit progression [2,8,9,10] (Figure 1)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
