Gourmet Lucie, Walker-Samuel Simon, Mallick Parag
Centre for Computational Medicine, Division of Medicine, University College London, London, United Kingdom.
Canary Center for Cancer Early Detection, Stanford University, Palo Alto, CA, United States.
Front Oncol. 2024 May 8;14:1406744. doi: 10.3389/fonc.2024.1406744. eCollection 2024.
Though the earliest stages of oncogenesis, post initiation, are not well understood, it is generally appreciated that a successful transition from a collection of dysregulated cells to an aggressive tumour requires complex ecological interactions between cancer cells and their environment. One key component of tumorigenesis is immune evasion. To investigate the interplay amongst the ecological behaviour of mutualism and immune evasion, we used a computational simulation framework. Sensitivity analyses of the growth of a virtual tumour implemented as a 2D-hexagonal lattice model suggests tumour survival depends on the interplay between growth rates, mutualism and immune evasion. In 60% of simulations, cancer clones with low growth rates, but exhibiting mutualism were able to evade the immune system and continue progressing suggesting that tumours with equivalent growth rates and no mutualism are more likely to be eliminated than tumours with mutualism. Tumours with faster growth rates showed a lower dependence upon mutualism for progression. Geostatistical analysis showed decreased spatial heterogeneity over time for polyclonal tumours with a high division rate. Overall, these results suggest that in slow growing tumours, mutualism is critical for early tumorigenesis.
尽管肿瘤发生起始后的最早阶段尚未完全明了，但人们普遍认识到，从一群失调细胞成功转变为侵袭性肿瘤需要癌细胞与其环境之间复杂的生态相互作用。肿瘤发生的一个关键组成部分是免疫逃逸。为了研究互利共生的生态行为与免疫逃逸之间的相互作用，我们使用了一个计算模拟框架。对作为二维六边形晶格模型实现的虚拟肿瘤生长的敏感性分析表明，肿瘤存活取决于生长速率、互利共生和免疫逃逸之间的相互作用。在60%的模拟中，生长速率低但表现出互利共生的癌症克隆能够逃避免疫系统并继续发展，这表明生长速率相同且无互利共生的肿瘤比有互利共生的肿瘤更有可能被消除。生长速率较快的肿瘤在进展过程中对互利共生的依赖性较低。地统计分析表明，具有高分裂率的多克隆肿瘤随时间推移空间异质性降低。总体而言，这些结果表明，在生长缓慢的肿瘤中，互利共生对早期肿瘤发生至关重要。
