Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE221448 | GEO | 2023/01/12
REPOSITORIES: GEO
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Project description:This study assess the role of HIFU on genetic change intratumorally post-treatment Immunotherapy promises unprecedented benefits to cancer patients. However, the majority of cancer types, including high-risk neuroblastoma remain immunologically unresponsive. High intensity focused ultrasound (HIFU) is a non-invasive technique that can mechanically fractionate tumors, transforming immunologically ‘‘cold’’ tumors into responsive ‘‘hot’’ tumors. We treated tumors with HIFU, and assessed systemic immune response using flow-cytometry, ELISA, and gene sequencing. In addition, we combined this treatment with αCTLA-4 and αPD-L1 to study its effect on the immune response and long-term survival. Combining HIFU with αCTLA-4 and αPD-L1 significantly enhances anti-tumor response, improving survival from 0 to 62.5%. HIFU alone causes upregulation of splenic and lymph node NK cells and circulating IL-2, IFN-Ɣ, and DAMPs, whereas immune regulators like CD4+Foxp3+, IL-10, and VEGF-A are significantly reduced. We also report significant abscopal effect following unilateral treatment of mice with large, established bilateral tumors using HIFU and checkpoint inhibitors compared to tumors treated with HIFU or checkpoint inhibitors alone (61.1% survival, p<0.0001). HIFU can effectively induce immune sensitization in a previously unresponsive murine neuroblastoma model, and promises a novel yet efficacious immuno-adjuvant modality to overcome therapeutic resistance.
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