Ultrasound-induced immunogenic cell death in cancer: mechanisms, immune remodeling, and therapeutic opportunities
4 affiliations
- 1Department of Ultrasound, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian, China
- 2Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian, China
- 3Department of Internal Medicine, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian, China
- 4Department of Gynecology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian, China
Abstract
Therapeutic ultrasound is emerging as a spatially controllable strategy for converting local tumor destruction into systemic antitumor immunity. Beyond direct cytotoxicity, sonodynamic therapy, ultrasound-targeted microbubble or nanobubble destruction, low-intensity focused ultrasound, and histotripsy can induce immunogenic cell death (ICD) through reactive oxygen species generation, endoplasmic reticulum stress, mitochondrial damage, cGAS-STING activation, pyroptosis, ferroptosis, and necroptosis. These processes promote calreticulin exposure, ATP secretion, HMGB1 release, tumor antigen liberation, dendritic-cell maturation, and CD8+ T-cell priming, thereby remodeling immune-suppressive tumor microenvironments and sensitizing tumors to immunotherapy. Recent experimental studies further show that ultrasound-responsive nanoplatforms can integrate sonosensitizers, chemotherapeutics, immune checkpoint inhibitors, STING agonists, cytokine mRNA, miRNA, or siRNA to amplify ICD and overcome immune resistance. However, clinical translation remains limited by heterogeneous ultrasound parameters, inconsistent ICD validation, complex nanomaterial design, and insufficient biomarker-guided patient selection. This review summarizes recent advances in ultrasound-induced ICD, highlights the immune mechanisms connecting tumor cell death with adaptive immunity, and discusses rational combination strategies with PD-1/PD-L1 blockade, STING activation, chemotherapy, and gene-based immunotherapy. We propose that future sono-immunotherapy should shift from maximizing tumor killing toward exploiting ultrasound-induced immune responses to create new therapeutic opportunities.
Related
- Tumor microenvironment-driven immune evasion in triple-negative breast cancer: mechanisms, clinical challenges, and therapeutic opportunities
- Stem cell factor in allergic diseases: mechanisms of type 2 immunity and therapeutic opportunities
- Itaconate as an immunometabolic hub in host-pathogen interactions: Mechanisms, resistance, and therapeutic opportunities.
- STAT3 at the tumor-immune interface: mechanisms of immune escape and therapeutic opportunities
- Engineered bacteria-mediated stromal remodeling in pancreatic ductal adenocarcinoma: therapeutic opportunities and translational limits-a narrative review.
BibTeX
@article{zhang2026ultrasoundinduced,
title = {{Ultrasound-induced immunogenic cell death in cancer: mechanisms, immune remodeling, and therapeutic opportunities}},
author = {Qiulan Zhang and Zhenhao Lan and Tao Wei and Guojin Lin and Meihong Xu and Xiaoyan Li and Yanni Bao},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1975744},
url = {https://doi.org/10.3389/fimmu.2026.1975744},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ultrasound-induced immunogenic cell death in cancer: mechanisms, immune remodeling, and therapeutic opportunities
AU - Qiulan Zhang
AU - Zhenhao Lan
AU - Tao Wei
AU - Guojin Lin
AU - Meihong Xu
AU - Xiaoyan Li
AU - Yanni Bao
PY - 2026
DA - 2026/11/09
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1975744
UR - https://doi.org/10.3389/fimmu.2026.1975744
AB - Therapeutic ultrasound is emerging as a spatially controllable strategy for converting local tumor destruction into systemic antitumor immunity. Beyond direct cytotoxicity, sonodynamic therapy, ultrasound-targeted microbubble or nanobubble destruction, low-intensity focused ultrasound, and histotripsy can induce immunogenic cell death (ICD) through reactive oxygen species generation, endoplasmic reticulum stress, mitochondrial damage, cGAS-STING activation, pyroptosis, ferroptosis, and necroptosis. These processes promote calreticulin exposure, ATP secretion, HMGB1 release, tumor antigen liberation, dendritic-cell maturation, and CD8+ T-cell priming, thereby remodeling immune-suppressive tumor microenvironments and sensitizing tumors to immunotherapy. Recent experimental studies further show that ultrasound-responsive nanoplatforms can integrate sonosensitizers, chemotherapeutics, immune checkpoint inhibitors, STING agonists, cytokine mRNA, miRNA, or siRNA to amplify ICD and overcome immune resistance. However, clinical translation remains limited by heterogeneous ultrasound parameters, inconsistent ICD validation, complex nanomaterial design, and insufficient biomarker-guided patient selection. This review summarizes recent advances in ultrasound-induced ICD, highlights the immune mechanisms connecting tumor cell death with adaptive immunity, and discusses rational combination strategies with PD-1/PD-L1 blockade, STING activation, chemotherapy, and gene-based immunotherapy. We propose that future sono-immunotherapy should shift from maximizing tumor killing toward exploiting ultrasound-induced immune responses to create new therapeutic opportunities.
SN - 1664-3224
ER -