由抗原突变积累决定的癌症免疫协同进化。

IF 6.4 1区 生物学 Q1 BIOLOGY
eLife Pub Date : 2025-10-10 DOI:10.7554/eLife.103970
Long Wang, Christo Morison, Weini Huang
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引用次数: 0

摘要

免疫系统是抵御癌症的第一道防线之一。当效应细胞试图抑制肿瘤时,癌细胞可以进化出逃避或抑制的方法。这种共同进化系统的知识可以帮助理解肿瘤发生和免疫治疗期间的肿瘤免疫动力学。在这里,我们提出了一个基于个体的突变积累模型,其中癌细胞中的随机突变触发专门的免疫反应。与以前的研究不同,我们明确地模拟了癌症和效应细胞之间的相互作用,并纳入了随机效应,这对小种群的扩张和灭绝很重要。我们发现控制癌症和效应细胞之间相互作用的参数诱导肿瘤进展的不同结果,如抑制和逃避。虽然很难直接测量癌症免疫动力学,但癌症的遗传信息可能表明这种相互作用的存在。我们的模型展示了在测序衍生的汇总统计中选择的特征,例如单细胞突变负担分布。因此,整体和单细胞测序可以提供有关共同进化动力学的信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cancer-immune coevolution dictated by antigenic mutation accumulation.

The immune system is one of the first lines of defence against cancer. When effector cells attempt to suppress tumour, cancer cells can evolve methods of escape or inhibition. Knowledge of this coevolutionary system can help to understand tumour-immune dynamics both during tumourigenesis and during immunotherapy treatments. Here, we present an individual-based model of mutation accumulation, where random mutations in cancer cells trigger specialised immune responses. Unlike previous research, we explicitly model interactions between cancer and effector cells and incorporate stochastic effects, which are important for the expansion and extinction of small populations. We find that the parameters governing interactions between the cancer and effector cells induce different outcomes of tumour progress, such as suppression and evasion. While it is hard to measure the cancer-immune dynamics directly, genetic information of the cancer may indicate the presence of such interactions. Our model demonstrates signatures of selection in sequencing-derived summary statistics, such as the single-cell mutational burden distribution. Thus, bulk and single-cell sequencing may provide information about the coevolutionary dynamics.

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来源期刊
eLife
eLife BIOLOGY-
CiteScore
12.90
自引率
3.90%
发文量
3122
审稿时长
17 weeks
期刊介绍: eLife is a distinguished, not-for-profit, peer-reviewed open access scientific journal that specializes in the fields of biomedical and life sciences. eLife is known for its selective publication process, which includes a variety of article types such as: Research Articles: Detailed reports of original research findings. Short Reports: Concise presentations of significant findings that do not warrant a full-length research article. Tools and Resources: Descriptions of new tools, technologies, or resources that facilitate scientific research. Research Advances: Brief reports on significant scientific advancements that have immediate implications for the field. Scientific Correspondence: Short communications that comment on or provide additional information related to published articles. Review Articles: Comprehensive overviews of a specific topic or field within the life sciences.
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