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抗血管生成药物的剂量与给药时间在联合放疗中对免疫细胞的影响
首发时间：2024-05-31
摘要：放疗常与抗血管生成药物进行联合治疗，而抗血管生成药物的不同给药方式如何影响联合治疗仍不很清楚。本研究运用原位肿瘤模型，分析了抗血管药物的剂量和给药时间在联合治疗中对肿瘤浸润免疫细胞的影响。在4t1肿瘤模型中，提高anlotinib的联合剂量降低了放疗所引起的t细胞肿瘤浸润，而提高了treg细胞的比例以及t细胞上pd1的表达水平。在eo771肿瘤模型中，放疗联合低剂量的anlotinib可以提高肿瘤浸润的t细胞、tams、和m-mdsc 的比例（单核型髓源抑制性细胞）的比例，而增加anlotinib的联合剂量则消除了这些作用。另外，放疗联合长期anlotinib治疗提高了两种模型中肿瘤浸润pmn-mdsc的比例。这些实验结果表明，放疗联合高剂量anlotinib或长时间anlotinib治疗容易增加肿瘤微环境的免疫抑制性，这可能削弱联合疗效和产生耐药性。
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the effects of dose and timing of anti-angiogenic therapy on intratumoral immune cells in its combination with radiotherapy
abstract：radiation therapy is often combined with anti-angiogenic drugs, and it is not clear how different modes of administration of antiangiogenic drugs affect combination therapy. in this study, two orthotopic tumor models were used to analyze the effects of the dosage and administration time of anlotinib on intratumoral immune cells in combination therapy. in 4t1 tumor model, increasing the dose of anlotinib in combination decreased radiotherapy-induced t cell tumor infiltration and increased the proportions of treg cells and pd1-expressing t cells. in eo771 tumor model, radiotherapy combined with low-dose anlotinib increased the proportions of tintraumoral t cells, tams, and m-mdscs (monocytic myeloid-derived suppressor cells), while increasing the combination dose of anlotinib eliminated these effects. in addition, long-term anlotinib combination therapy increased the proportions of intratumoral pmn-mdsc (polymorphonuclear myeloid-derived suppressor cells) in both models. these results suggest that radiotherapy in combination with higher doses of or longer-term anlotinib therapy is more likely to increase the immunosuppressive properties of the tumor microenvironment, which may compromise combination efficacy and induce drug resistance.
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抗血管生成药物的剂量与给药时间在联合放疗中对免疫细胞的影响
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