Biological Mechanisms of Microwave Ablation in Thyroid Tumors and Its Induced Immunomodulatory Effects

Zhaoyin Wang,1 Qingquan Dai,1 Shaozhang Yan,1 Xinyue Sun,2 Gang Wang,2 Ziwei He,3 Yinxiong He,1 Zhe Wang,4 Liwei Wang,1 Chuang Liu,1 Tingting Liu,1 Ruiyun Gao,1 Puguang Zhao,1 Kuanyu Wang2 1Graduate School, Heilongjiang University of Traditional Chinese Medicine, Harbin, People’s Republic of China; 2The Second Department of Surgery, The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, People’s Republic of China; 3Medical Affairs Department, The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, People’s Republic of China; 4Endoscopic Diagnosis and Treatment Center, The Third Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, People’s Republic of ChinaCorrespondence: Kuanyu Wang, The Second Department of Surgery, The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, People’s Republic of China, Email wangkuanyu_1964@163.comAbstract: Microwave ablation (MWA) is a minimally invasive thermal ablation technique that eradicates thyroid tumors by rapidly increasing tissue temperature to 60– 100 degrees Celsius (°C) through dielectric hysteresis. This focused electromagnetic heating leads to irreversible protein denaturation, cell membrane disruption, and coagulative necrosis. Within the ablation zone, mitochondria and the endoplasmic reticulum sustain severe thermal injury accompanied by DNA double-strand breaks. The resulting cell death occurs via apoptosis, pyroptosis, and ferroptosis, while necrotic tissue triggers a robust inflammatory response that facilitates debris clearance and tissue remodeling. Damage-associated molecular patterns (DAMPs) and heat shock proteins (HSPs), released from dying cells, mediate immunogenic cell death (ICD) and promote dendritic cell activation and cytotoxic T lymphocyte (CTL) responses, leading to systemic antitumor immunity. Moreover, thermal injury disrupts the local vasculature, resulting in transient ischemia and hypoxia that activate the hypoxia-inducible factor-1 alpha (HIF-1α) pathway and stimulate vascular repair and fibrosis through transforming growth factor-beta (TGF-β) and vascular endothelial growth factor (VEGF) signaling. In addition, peripheral immune alterations and immune-related gene activation suggest potential synergy between MWA and immune checkpoint blockade. Collectively, MWA not only provides effective local tumor destruction but also reshapes the tumor immune microenvironment, offering a rationale for combined thermal and immunotherapeutic strategies in thyroid oncology. Keywords: microwave ablation, thyroid tumors, papillary thyroid carcinoma, biological mechanisms, immunomodulation