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微波消融后Lewis肺癌小鼠模型肿瘤引流淋巴结免疫微环境的动态变化

Dynamic Changes in the Immune Microenvironment in Tumor-Draining Lymph Nodes of a Lewis Lung Cancer Mouse Model After Microwave Ablation.

作者信息

Sang Jing, Liu Peng, Wang Meixiang, Xu Fengkuo, Ma Ji, Wei Zhigang, Ye Xin

机构信息

Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, People's Republic of China.

Department of Pathology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, People's Republic of China.

出版信息

J Inflamm Res. 2024 Jul 1;17:4175-4186. doi: 10.2147/JIR.S462650. eCollection 2024.

Abstract

PURPOSE

Microwave ablation (MWA) is a minimally invasive technique for treating lung cancer. It can induce immune response; however, its effect on the immune microenvironment in tumor-draining lymph nodes (TdLN) is not well understood. This study aims to identify changes in the immune microenvironment in TdLN following MWA in a Lewis lung cancer (LLC) mouse model.

METHODS

LLC mouse model was established and followed by MWA. TdLN were collected at various time points, including pre-MWA and days 1, 2, 4, and 8 post-MWA. Flow cytometry was used to determine the frequencies of CD4 T cells, CD8 T cells, regulatory T (Treg) cells, natural killer (NK) cells, dendritic cells (DCs) and other immune cells in the TdLN. Certain cytokines were also detected.

RESULTS

Compared with pre-MWA, the frequency of CD4 T cells significantly increased from day 1 to day 8 post-MWA. The frequency of CD8 T cells decreased significantly on days 2 and 4, but no significant changes occurred on days 1 and 8. Significant decreases in the frequencies of Treg cells and Klrg1 Treg cells were observed from day 1 to day 4. On days 4 and 8, there was a significant increase in the frequency of NK cells. The frequency of resident cDC2 significantly increased on day 4, whereas CD11b migratory cDCs increased on day 1. Additionally, on day 4, a notable rise was observed in the frequency of NK cells secreting IFN-γ, while on day 8, there was a significant increase in the frequency of CD8 T cells secreting both IFN-γ and TNF-α.

CONCLUSION

MWA of lung cancer can alter the immune microenvironment in the TdLN, triggering immune responses. These changes are particularly evident and intricate within the initial 4 days post-MWA. Treatment combined with MWA within a certain period may significantly enhance anti-tumor immunity.

摘要

目的

微波消融(MWA)是一种治疗肺癌的微创技术。它可诱导免疫反应;然而,其对肿瘤引流淋巴结(TdLN)中免疫微环境的影响尚不清楚。本研究旨在确定Lewis肺癌(LLC)小鼠模型中MWA后TdLN免疫微环境的变化。

方法

建立LLC小鼠模型并进行MWA。在包括MWA前以及MWA后第1、2、4和8天等不同时间点收集TdLN。采用流式细胞术测定TdLN中CD4 T细胞、CD8 T细胞、调节性T(Treg)细胞、自然杀伤(NK)细胞、树突状细胞(DC)及其他免疫细胞的频率。还检测了某些细胞因子。

结果

与MWA前相比,MWA后第1天至第8天CD4 T细胞频率显著增加。CD8 T细胞频率在第2天和第4天显著降低,但在第1天和第8天无显著变化。从第1天到第4天观察到Treg细胞和Klrg1 Treg细胞频率显著降低。在第4天和第8天,NK细胞频率显著增加。驻留cDC2频率在第4天显著增加,而CD11b迁移性cDC在第1天增加。此外,在第4天,分泌IFN-γ的NK细胞频率显著升高,而在第8天,分泌IFN-γ和TNF-α的CD8 T细胞频率显著增加。

结论

肺癌的MWA可改变TdLN中的免疫微环境,引发免疫反应。这些变化在MWA后最初4天内尤为明显和复杂。在一定时期内联合MWA治疗可能显著增强抗肿瘤免疫力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98f/11228081/61b3b286b08e/JIR-17-4175-g0001.jpg

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