热消融（TA），包括射频消融（RFA）和微波消融（MWA）可以减轻肿瘤负荷并可以刺激免疫反应，但它不能维持持久的免疫反应。令人震惊的细胞因子 IL-33 由上皮细胞、内皮细胞和成纤维细胞组成型表达，但在组织损伤期间释放以警告免疫系统。 TME 中 ST2 Tregs 的存在可能充当导致这种现象的屏障。在这项研究中，我们探讨了 RFA 对肿瘤浸润淋巴细胞 (TIL) 中 ST2（也称为 IL1RL1）表达的影响。随后，我们构建了Treg细胞特异性缺失ST2小鼠模型（Foxp3CreIl1rl1fl/fl），并通过流式细胞术评估了遗传表型。建立Foxp3Cre和Foxp3CreIl1rl1fl/fl小鼠双侧背侧荷瘤模型，探讨MWA的抗肿瘤作用。最后，我们使用流式细胞术和单细胞转录组测序 (scRNA-seq) 来分析 TME 内的 CD45 免疫细胞。我们的研究结果表明，消融上调了对侧 TME 内 Tregs 中的 ST2 表达。与Foxp3Cre小鼠相比，MWA显着抑制Foxp3CreIl1rl1fl/fl小鼠对侧肿瘤的生长。其机制包括减少Tregs的比例，增强CD8 T细胞的浸润和效应功能，增加效应CD8 T细胞的比例，减少Exhausted CD8 T细胞的比例，增加mDC细胞和单核细胞中的MHC-I分子，以及降低 TAM2 抑制分子和趋化因子的表达。阻断 Tregs 中的 IL-33/ST2 通路为转移性癌症临床研究中的 MWA 提供了新策略。版权所有 © 2024 Elsevier B.V. 保留所有权利。

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.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.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.Blocking IL-33/ST2 pathway in Tregs offers a new strategy for MWA in clinical studies of metastatic cancer.Copyright © 2024 Elsevier B.V. All rights reserved.