不同加热参数的原发性肿瘤微波消融后在 VX2 肿瘤模型中的不同免疫反应。

Distinct immunoreactions after a primary tumor microwave ablation using different heating parameters in a VX2 tumor model.

机构信息

Department of Thyroid and Breast Surgery, The Affiliated JiangNing Hospital of Nanjing Medical University, Nanjing, People's Republic of China.

Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.

出版信息

J Cancer Res Ther. 2023 Dec 1;19(6):1620-1626. doi: 10.4103/jcrt.jcrt_502_23. Epub 2023 Dec 28.

DOI:10.4103/jcrt.jcrt_502_23

PMID:38156930

Abstract

BACKGROUND

Thermal ablation of solid tumors in situ can activate the immune system and produce a specific immune response against the tumor. Microwave ablation (MWA) with different parameters can ablate tumors with similar sizes and cause different local inflammatory effects. Our aim was to determine the immunological effects induced by different energy modes of MWA for a primary tumor.

METHODS

Seventy rabbits with VX2 tumors that were implanted subcutaneously underneath the right second nipple were treated with high-power MWA (40 W for 1 min), low-power MWA (20 W for 2 min), or surgical resection or were left without treatment (control). Survival time was evaluated by log-rank test. On day 14 after ablation, immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses. In addition, the cytokine patterns were identified by enzyme-linked immunosorbent assay.

RESULTS

Tumor eradication was achieved completely in the MWA groups, as proven by nicotinamide adenine dinucleotide diaphorase staining. Compared with the three treatment groups, the control group had a significantly higher number of pulmonary metastases and worse survival; however, no significant difference was observed among the three treatment groups. More intra-tumoral and systemic CD4+ and CD8+ T-cells were induced in the MWA groups than in the control group. Compared with operation, MWA induced more systemic CD4+ T-cells. More intra-tumoral CD4+ and CD8+ T-cells and systemic CD4+ T-cells were induced by high-power MWA than by low-power MWA. Moreover, MWA increased the interleukin 2 (IL2) and IL12 levels and decreased the IL4, IL6, and IL10 levels. Importantly, the serum IL12 level was significantly higher after high-power MWA than after low-power MWA.

CONCLUSION

High-power MWA enhanced the type 1 T helper immune response and may be selected for the treatment of solid tumors. Future studies are needed to confirm our results.

摘要

背景

实体肿瘤的原位热消融可以激活免疫系统，对肿瘤产生特异性免疫反应。不同参数的微波消融（MWA）可以消融大小相似的肿瘤，并引起不同的局部炎症反应。我们的目的是确定 MWA 不同能量模式对原发性肿瘤引起的免疫效应。

方法

70 只皮下接种 VX2 肿瘤于右侧第二乳头下的兔子，分别接受高功率 MWA（40 W 持续 1 分钟）、低功率 MWA（20 W 持续 2 分钟）、手术切除或不治疗（对照组）。用对数秩检验评估生存时间。消融后 14 天，用免疫组织化学和流式细胞术评估 T 细胞免疫反应。此外，通过酶联免疫吸附试验确定细胞因子模式。

结果

MWA 组完全消除了肿瘤，烟酰胺腺嘌呤二核苷酸脱氢酶染色证实了这一点。与三组治疗组相比，对照组的肺转移数量明显更高，生存状况更差；但三组治疗组之间无显著差异。与对照组相比，MWA 组的肿瘤内和全身 CD4+和 CD8+T 细胞数量更多。与手术相比，MWA 诱导更多的全身 CD4+T 细胞。与低功率 MWA 相比，高功率 MWA 诱导更多的肿瘤内 CD4+和 CD8+T 细胞和全身 CD4+T 细胞。此外，MWA 增加了白细胞介素 2（IL2）和白细胞介素 12（IL12）水平，降低了白细胞介素 4（IL4）、白细胞介素 6（IL6）和白细胞介素 10（IL10）水平。重要的是，高功率 MWA 后血清 IL12 水平明显高于低功率 MWA 后。