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Published on: June 4, 2021
Immunological Effects of Histotripsy for Cancer Therapy
Alissa Hendricks-Wenger1,2,3, Ruby Hutchison3, Eli Vlaisavljevich1,3,4
1Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Roanoke, VA, United States.
Abstract:
Cancer is the second leading cause of death worldwide despite major advancements in diagnosis and therapy over the past century. One of the most debilitating aspects of cancer is the burden brought on by metastatic disease. Therefore, an ideal treatment protocol would address not only debulking larger primary tumors but also circulating tumor cells and distant metastases. To address this need, the use of immune modulating therapies has become a pillar in the oncology armamentarium. A therapeutic option that has recently emerged is the use of focal ablation therapies that can destroy a tumor through various physical or mechanical mechanisms and release a cellular lysate with the potential to stimulate an immune response. Histotripsy is a non-invasive, non-ionizing, non-thermal, ultrasound guided ablation technology that has shown promise over the past decade as a debulking therapy. As histotripsy therapies have developed, the full picture of the accompanying immune response has revealed a wide range of immunogenic mechanisms that include DAMP and anti-tumor mediator release, changes in local cellular immune populations, development of a systemic immune response, and therapeutic synergism with the inclusion of checkpoint inhibitor therapies. These studies also suggest that there is an immune effect from histotripsy therapies across multiple murine tumor types that may be reproducible. Overall, the effects of histotripsy on tumors show a positive effect on immunomodulation.
Insights
Histotripsy, an ultrasound-guided ablation therapy, effectively debulks tumors and stimulates an anti-cancer immune response. This approach shows promise for treating metastatic cancer by enhancing the body's natural defenses.
Area of Science:
- Oncology
- Immunology
- Medical Physics
Background:
- Cancer remains a leading cause of death, with metastasis posing a significant challenge.
- Current treatments focus on debulking tumors but often fail to address circulating tumor cells and distant metastases.
- Immune-modulating therapies are crucial in oncology, and focal ablation offers a novel approach.
Purpose of the Study:
- To investigate the immunomodulatory effects of histotripsy, an ultrasound-guided ablation technology.
- To assess histotripsy's potential to stimulate an anti-cancer immune response beyond tumor debulking.
- To explore the therapeutic synergy of histotripsy with other cancer treatments.
Main Methods:
- Histotripsy, a non-invasive, non-thermal ultrasound ablation technique, was employed to treat tumors.
- The study analyzed the immune response triggered by histotripsy, including cellular changes and mediator release.
- Investigated the efficacy of histotripsy across various murine tumor models.
Main Results:
- Histotripsy demonstrated significant tumor debulking capabilities.
- The therapy induced a range of immunogenic mechanisms, including the release of damage-associated molecular patterns (DAMPs) and anti-tumor mediators.
- Observed changes in local immune cell populations and the development of a systemic immune response.
- Histotripsy showed therapeutic synergism with checkpoint inhibitor therapies.
Conclusions:
- Histotripsy is a promising focal ablation therapy with significant immunomodulatory effects.
- The technology has the potential to stimulate a comprehensive anti-cancer immune response, addressing both primary tumors and potential metastases.
- Histotripsy's immune-stimulating properties may be reproducible across different cancer types, offering a new avenue for cancer treatment.
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