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

Abstract

Jing Sang,1,2,* Peng Liu,1,3,* Meixiang Wang,1 Fengkuo Xu,1 Ji Ma,1 Zhigang Wei,1 Xin Ye1 1Department 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; 2Department of Pathology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, People’s Republic of China; 3Yuncheng Central Hospital Affiliated to Shanxi Medical University, Yuncheng, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhigang Wei; Xin Ye, Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, 250014, People’s Republic of China, Email [email protected]; [email protected]: 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.Keywords: microwave ablation, lung cancer, T cells, regulatory T cells, natural killer cells, dendritic cells

Keywords

• microwave ablation
• lung cancer
• t cells
• regulatory t cells
• natural killer cells
• dendritic cells