Related Experiment Video
Updated: Jun 10, 2025
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Tregs ST2 deficiency enhances the abscopal anti-tumor response induced by microwave ablation
Shaoxian Wu1, Jing Jiao2, Nuo Wang1
1Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, China.
Background:
Thermal ablation (TA), including radiofrequency ablation (RFA) and Microwave ablation (MWA) could reduce tumor burden and can stimulate an immune response, but it cannot maintain a lasting immune response. The alarming cytokine IL-33 is constitutively expressed by epithelial cells, endothelial cells, and fibroblasts, but is released during tissue injury to alert the immune system. The presence of ST2+Tregs in TME may act as a barrier contributing to this phenomenon.
Methods:
In this study, we explored the impact of RFA on the expression of ST2 (also known as IL1RL1) in tumor-infiltrating lymphocytes (TILs). Subsequently, we constructed a Treg cell-specific deletion ST2 mouse model (Foxp3CreIl1rl1fl/fl) and evaluated the genetic phenotypes by flow cytometry. A bilateral dorsal tumor-bearing model was established in Foxp3Cre and Foxp3CreIl1rl1fl/fl mice to explore the anti-tumor effect of MWA. Finally, we used flow cytometry and single-cell transcriptome sequencing (scRNA-seq) to profile CD45+ immune cells within TME.
Results:
Our findings suggest that ablation upregulates ST2 expression in Tregs within the contralateral TME. Compared with Foxp3Cre mice, MWA significantly inhibited the growth of contralateral tumors in Foxp3CreIl1rl1fl/fl mice. Its mechanisms include reducing the proportion of Tregs, enhancing the infiltration and effector function of CD8+T cells, increasing the proportion of Effector CD8+T cells, reducing the proportion of Exhausted CD8+T cells, increasing MHC-I molecules in mDC cells and monocytes, and reducing the expression of TAM2 inhibitory molecules and chemokines.
Conclusions:
Blocking IL-33/ST2 pathway in Tregs offers a new strategy for MWA in clinical studies of metastatic cancer.
