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肿瘤特异性免疫增强作用后局部冷冻消融治疗转移性骨肿瘤的小鼠模型。

Tumor-Specific Immunoenhancing Effects after Local Cryoablation for Metastatic Bone Tumor in a Mouse Model.

机构信息

Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.

Department of Radiology, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.

出版信息

Int J Mol Sci. 2022 Aug 21;23(16):9445. doi: 10.3390/ijms23169445.

DOI:10.3390/ijms23169445
PMID:36012709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9409399/
Abstract

We investigated the abscopal effect after cryoablation (CA) on bone metastasis using a mouse model. Breast cancer cells were implanted in the bilateral tibiae of mice. The left tumor was treated locally with CA, and the right abscopal tumor (AT) was left untreated. The mice were divided into four groups based on the combination of CA and intraperitoneal administration of anti-PD-1 antibody (PD) as treatment interventions (Control, CA, PD, and CA + PD). The reduction ratio of the size of AT, the quantitative immune effects at enzyme-linked immunospot (ELISPOT) assay, and the intensity of infiltration of immune-related cells to AT were compared among the groups. CA alone showed a significant immunoenhancing effect on the volume change ratio of AT from day 0 to day 14 (Control-CA: p < 0.05), ELISPOT assay (Control-CA: p < 0.01), and CD4+ cell count in immunostaining (Control-CA: p < 0.05). CA alone showed no significant immunoenhancing effect on CD8+ and Foxp3+ cell counts in immunostaining, but the combination of CA and PD showed a significant immunoenhancing effect (Control-CA + PD: p < 0.01 [CD8, Foxp3]). The results suggested that the abscopal effect associated with the local cryotherapy of metastatic bone tumors was activated by CA and enhanced by its combination with PD.

摘要

我们使用小鼠模型研究了冷冻消融（CA）后骨转移的远隔效应。将乳腺癌细胞植入小鼠双侧胫骨中。左侧肿瘤局部接受 CA 治疗，右侧远隔肿瘤（AT）未接受治疗。根据 CA 和腹腔内给予抗 PD-1 抗体（PD）联合治疗干预的组合，将小鼠分为四组（对照组、CA 组、PD 组和 CA + PD 组）。比较各组 AT 大小的缩小率、酶联免疫斑点（ELISPOT）测定的定量免疫效应以及免疫相关细胞对 AT 的浸润强度。CA 单独治疗对 AT 体积变化比从第 0 天到第 14 天具有显著的免疫增强作用（对照组-CA：p < 0.05），ELISPOT 测定（对照组-CA：p < 0.01）和免疫染色中的 CD4+细胞计数（对照组-CA：p < 0.05）。CA 单独治疗对免疫染色中 CD8+和 Foxp3+细胞计数无显著免疫增强作用，但 CA 与 PD 联合使用显示出显著的免疫增强作用（对照组-CA + PD：p < 0.01[CD8，Foxp3]）。结果表明，与转移性骨肿瘤局部冷冻治疗相关的远隔效应被 CA 激活，并通过其与 PD 的联合增强。

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