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肿瘤细胞异质性对放射治疗的影响
首发时间：2024-06-12
摘要：肿瘤细胞异质性是导致肿瘤治疗耐药的一个重要原因，其在癌基因靶向治疗中的耐药机制已获得了深入的研究，而肿瘤细胞异质性如何影响放疗的疗效，仍是一个尚待探索的问题。通过建立小鼠eo771乳腺肿瘤细胞系的单细胞克隆 (single cell clones, sccs)，并进行放射治疗，实验结果显示：各种scc肿瘤模型对放疗的敏感性呈现异质性，可根据肿瘤生长抑制率tgi（tumor growth inhibition）分为放疗敏感型和放疗耐受型sccs。由同种类型scc混合形成的肿瘤，对放疗的敏感性不变；而由不同类型scc混合形成的肿瘤模型，在放疗敏感性上更类似于耐受型scc肿瘤模型。放疗对这些肿瘤模型中cd8 t细胞的比例、肿瘤血管密度与功能均没有显著的一致性的影响。但是，各种scc及各种混合形成的肿瘤模型在放疗前，放疗敏感型肿瘤的血管灌注功能显著高于放疗耐受型肿瘤。这些结果表明肿瘤细胞异质性对放疗疗效的影响取决肿瘤细胞克隆的性质，而不是数量，而放疗耐受型克隆在其中发挥主导作用，其机制可能是通过降低肿瘤血管的灌注功能来削弱放疗效果。
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the effects of tumor cell heterogeneity on radiotherapy
abstract：tumor cell heterogeneity is a crucial factor contributing to cancer treatment resistance. although its resistance mechanisms in oncogen targeted therapy have been extensively investigated, how tumor cell heterogeneity affects on the efficacy of radiotherapy remains largely unknown.the tumors derived from single-cell clones (sccs) isolated from mouse eo771 breast tumor cell lines were treated with radiotherapy. the responses of various scc breast tumor models to radiotherapy were heterogeneous, which were classified as radiotherapy-sensitive and radiotherapy-resistant types based on the values of tumor growth inhibition. tumor models derived from mixing the same type of sccs exhibited similar radiotherapy sensitivity to the premixing scc tumor models, but tumor models derived from mixing different types of sccs were resistant to radiotherapy, which was similar to the premixing radiotherapy-resistant scc tumor models. radiotherapy did not show consistent and significant impacts on the proportions of cd8 t cells, tumor vessel density, and vascular perfusion in these tumor models. however, before radiotherapy, vascular perfusion in the radiotherapy-sensitive tumor models of various sccs and their combinations was significantly higher than that of radiotherapy-resistant tumor models. these results suggest that the impacts of tumor cell heterogeneity on radiotherapy sensitivity are determined by the characteristics of tumor cell clones, but not the quantity of tumor cell clones. among them, radiotherapy-resistant clones exert a predominant influence, potentially through the reduction of tumor vessel perfusion.
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