Mondini M, Guipaud O, François A, Mathieu N, Deutsch É, Milliat F
Gustave-Roussy, Inserm U1030, université Paris-Saclay, Villejuif, France.
Institut de radioprotection et de sûreté nucléaire (IRSN), PSE-Sante/Seramed/LRMed, 92260 Fontenay-aux-Roses, France.
Cancer Radiother. 2023 Sep;27(6-7):643-647. doi: 10.1016/j.canrad.2023.06.013. Epub 2023 Jul 27.
Radiation-induced toxicity of the digestive tract is a major clinical concern as many cancer survivors have received radiotherapy for tumours of the abdominopelvic area. The coordination and orchestration of a tissue's response to stress depend not only on the phenotype of the cells that make up the tissue but also on cell-cell interactions. The digestive system, i.e., the intestine/colon/rectum, is made up of a range of different cell populations: epithelial cells, stromal cells, i.e. endothelial cells and mesenchymal lineages, immune cells and nerve cells. Moreover, each of these populations is heterogeneous and presents very significant plasticity and differentiation states. The pathogenesis of radiation-induced digestive lesions is an integrated process that involves multiple cellular compartments interacting in a complex sequence of events. Understanding all the cellular events and communication networks that contribute to the tissue's response to stress is therefore a major conceptual and methodological scientific challenge. The study of heterogeneous populations of cells in a tissue is now possible thanks to "single cell' RNA sequencing and spatial transcriptomics techniques, which enable a comprehensive study of the transcriptomic profiles of individual cells in an integrated system. In addition, the mathematical and bioinformatics tools that are now available for the large-scale analysis of data allow the inference of cell-cell communication networks. Such approaches have become possible through advances in bioinformatics algorithms for the analysis and deciphering of interaction networks. Interactions influence the tissue regeneration process through expression of various molecules, including metabolites, integrins, junction proteins, ligands, receptors and proteins secreted into the extracellular space. The vascular network is viewed as a key player in the progression of digestive lesions, which are characterised by infiltration of a range of immune cells. A better characterisation of endothelium/immune cell interactions in suitable preclinical models, as well as in humans, may help to identify some promising therapeutic targets for the prediction, prevention or treatment of digestive toxicity after radiotherapy.
由于许多癌症幸存者都接受过针对腹部盆腔区域肿瘤的放射治疗，因此放射性消化道毒性是一个主要的临床问题。组织对压力的反应的协调和调控不仅取决于构成组织的细胞的表型，还取决于细胞间的相互作用。消化系统，即肠道/结肠/直肠，由一系列不同的细胞群体组成：上皮细胞、基质细胞，即内皮细胞和间充质谱系细胞、免疫细胞和神经细胞。此外，这些群体中的每一个都是异质性的，并且呈现出非常显著的可塑性和分化状态。放射性消化损伤的发病机制是一个综合过程，涉及多个细胞区室在一系列复杂事件中相互作用。因此，了解所有导致组织对压力作出反应的细胞事件和通讯网络是一项重大的概念和方法学科学挑战。借助“单细胞”RNA测序和空间转录组学技术，现在可以对组织中的异质性细胞群体进行研究，这些技术能够在一个综合系统中全面研究单个细胞的转录组图谱。此外，现在可用于大规模数据分析的数学和生物信息学工具允许推断细胞间通讯网络。通过生物信息学算法在分析和破译相互作用网络方面的进展，此类方法已成为可能。相互作用通过各种分子的表达影响组织再生过程，这些分子包括代谢物、整合素、连接蛋白、配体、受体和分泌到细胞外空间的蛋白质。血管网络被视为消化损伤进展中的关键因素，消化损伤的特征是一系列免疫细胞的浸润。在合适的临床前模型以及人类中更好地表征内皮细胞/免疫细胞相互作用，可能有助于确定一些有前景的治疗靶点，用于预测、预防或治疗放疗后的消化道毒性。
