Histotripsy stimulates the immune system to attack cancer cells outside the liver

Since FDA approval late 2023, the non-invasive liver tumor treatment, histotripsy has been used at University of Michigan Health since early 2024.

As the use of histotripsy is expanding across the state of Michigan and to surrounding states, U-M researchers are continuously observing the body’s immune response to histotripsy treatment.

Anutosh Ganguly, Ph.D., an assistant research scientist at University of Michigan Health led a team of researchers looking to extend beyond the characterization of immune responses following liver cancer treatment in hopes to expand the understanding of how histotripsy could impact other tumor types such as those found in pancreatic cancers and melanoma.

The technology, pioneered by biomedical engineers at U-M, uses ultrasound waves to destroy tumors within the liver without the major side effects experienced in other forms of cancer treatment such as chemotherapy and radiation.

Ganguly and the team’s data showed that immunomodulatory effects of histotripsy are most likely triggered by a reduction of tumor hypoxia, also known very low oxygen levels within the tumor. These low oxygen levels are no longer present after histotripsy treatment.

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“The relief from hypoxia after histotripsy treatment facilitates a rise in anti-tumor CD8+ T cells that move to the site of the procedure but also to the distant tumors within other parts of the body to oppose their growth,” said Ganguly.

“So, in addition to physically destroying tumor cells, histotripsy stimulates the patient’s own immune system to fight cancer more effectively throughout the body.”

Understanding that histotripsy treatment can alter how the body reacts to cancer cells located outside the liver gives better insight into how metastases in other areas of the body may respond to direct histotripsy treatment.

“The additional effect of activating the patient’s own immune system against cancer cells by histotripsy can help the patient’s body respond better to other types of cancer treatment they may be receiving in addition to the histotripsy such as radiation and chemotherapy,” said Ganguly.

SEE ALSO: Tumor-destroying soundwaves receive FDA approval for liver treatment in humans

“Our work to continue understanding the ways that histotripsy impacts the whole body can open doors for new and potentially more effective ways to treat cancer that have less patient side effects.”

Ganguly and his team plan to continue their study to gather further data on how histotripsy treatment impacts cancer cells within the entire body, the immune system of the patient and what additional therapies can enhance the results of histotripsy treatment.

Additional authors: Brian Song, Chaitanya Karanam, Natalie Gatteno and Katherine Buglak from the Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan and the Research Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan. Heineken Queen from the Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, the Research Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, and the Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, Michigan. Sarah F. Ferris from the Research Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan and the College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan. Reliza McGinnis, Hanna Kim and Zhen Xu from the Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan. Jinato Xu, Kristie D. Goughenour and Michael A. Olszweski from the Research Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan and the Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan. Clifford S. Cho from the Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, the Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, Michigan and the Department of Cell Biology, Van Andel Institute, Grand Rapids, Michigan.

Funding/disclosures: Our work was partially supported by HistoSonics who supported studies outside the submitted work and a patent issued, licensed, and with royalties paid from HistoSonics, Drs. Xu and Cho and by Focused Ultrasound Foundation. Apart from this, our studies were supported by multiple grants form National Institutes of Health and funding from the Department of Veterans Affairs that supported the conduct of the study and/or personnel involved in this work. All these potential COIs have been disclosed and reviewed by the research site institutions (University of Michigan, the Ann Arbor VA Medical Center) and were reported in all our publications that resulted from this work.

Paper cited: “Histotripsy-Focused Ultrasound Treatment Abrogates Tumor Hypoxia Responses and Stimulates Antitumor Immune Responses in Melanoma,” Molecular Cancer Therapeutics. DOI: 10.1158/1535-7163.MCT-24-0715