A race between tumor immunoescape and genome maintenance selects for optimum levels of (epi)genetic instability

Shingo Iwami, Hiroshi Haeno, Franziska Michor

研究成果: ジャーナルへの寄稿記事

8 引用 (Scopus)

抄録

The human immune system functions to provide continuous body-wide surveillance to detect and eliminate foreign agents such as bacteria and viruses as well as the body's own cells that undergo malignant transformation. To counteract this surveillance, tumor cells evolve mechanisms to evade elimination by the immune system; this tumor immunoescape leads to continuous tumor expansion, albeit potentially with a different composition of the tumor cell population ("immunoediting"). Tumor immunoescape and immunoediting are products of an evolutionary process and are hence driven by mutation and selection. Higher mutation rates allow cells to more rapidly acquire new phenotypes that help evade the immune system, but also harbor the risk of an inability to maintain essential genome structure and functions, thereby leading to an error catastrophe. In this paper, we designed a novel mathematical framework, based upon the quasispecies model, to study the effects of tumor immunoediting and the evolution of (epi)genetic instability on the abundance of tumor and immune system cells. We found that there exists an optimum number of tumor variants and an optimum magnitude of mutation rates that maximize tumor progression despite an active immune response. Our findings provide insights into the dynamics of tumorigenesis during immune system attacks and help guide the choice of treatment strategies that best inhibit diverse tumor cell populations.

元の言語英語
記事番号e1002370
ジャーナルPLoS Computational Biology
8
発行部数2
DOI
出版物ステータス出版済み - 2 1 2012

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tumor
Tumors
Tumor
Maintenance
Genome
genome
Genes
immune system
neoplasms
Immune system
Immune System
Neoplasms
mutation
Mutation
Cell Population
Cell
Cells
Mutation Rate
Surveillance
monitoring

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Modelling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

これを引用

A race between tumor immunoescape and genome maintenance selects for optimum levels of (epi)genetic instability. / Iwami, Shingo; Haeno, Hiroshi; Michor, Franziska.

:: PLoS Computational Biology, 巻 8, 番号 2, e1002370, 01.02.2012.

研究成果: ジャーナルへの寄稿記事

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