a race between tumor immunoescape and genome maintenance selects for optimum levels of (epi)genetic instability肿瘤immunoescape和基因组之间的种族维修选择最佳水平(epi)的遗传不稳定.pdfVIP

A Race between Tumor Immunoescape and Genome Maintenance Selects for Optimum Levels of (epi)genetic Instability 1. 2. 2 Shingo Iwami , Hiroshi Haeno , Franziska Michor * 1 PRESTO, Japan Science and Technology Agency, Graduate School of Mathematical Sciences, The University of Tokyo, Institute for Virus Research, Kyoto University, Kyoto, Japan, 2 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America Abstract 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 varia