Sound waves turn immune system into cancer fighter

Researchers at the University of Michigan have discovered how a treatment that uses ultrasound to destroy liver tumors can transform the body’s immune system into a fight against cancer.

FDA-approved technology not only physically destroys cancer cells. It fundamentally changes the tumor environment to help immune cells hunt cancer throughout the body. This dual action can reshape how doctors receive cancer treatment, providing new hope for patients with advanced disease who have spread to one location.

Beyond Body Destruction

Since early 2024, the University of Michigan’s Health University has been using tissue therapy to treat liver tumors after approval of the FDA at the end of 2023. The technology mechanically destroys tumor tissue by focusing ultrasound waves to create air bubbles without the severe side effects of chemotherapy or radiation.

But Dr. Anutosh Ganguly and his research team discovered unexpected situations that occurred after treatment. Ultrasound is not just about destroying tumors, they are producing diseases that awaken patients’ immune systems to fight cancer more effectively.

“Relieving hypoxia after tissue therapy promotes the increase of anti-tumor CD8+ T cells, which move to the surgical site and also promotes tumors distant inside other parts of the body to oppose their growth,” Ganguly said.

Oxygen connection

The key to the immune effect of tissue therapy is that tumors are hypoxia-high oxygen levels create a hostile environment for immune cells. Cancer tumors usually maintain these oxygen-starved diseases as survival strategies, which makes it difficult for the body’s natural defense to penetrate and attack.

Ganguly’s team found that tissue therapy treatment quickly eliminated tumor hypoxia. When oxygen levels return to normal, it triggers a series of changes that transform the tumor from an immunosuppressive environment to an environment where anti-cancer cells can reproduce.

The study, published in molecular cancer therapy, focuses on melanoma models, but has implications for other cancer types, including pancreatic cancer. What makes this discovery particularly exciting is that immune activation affects not only the treated tumor, but also the cancer cells throughout the body.

How Immune Awakening Works

This study reveals the complex biological mechanisms behind the immune effects of Histotipsy:

• Eliminate hypoxia: Ultrasound restores normal oxygen levels in tumors
• HIF1α inhibition: Reduced hypoxia shuts off survival proteins that help cancer cells escape immune detection
• CXCL10 up-regulation: Tumors begin to generate signals that attract immune cells
• CD8+ T cell infiltration: Anti-cancer immune cells flood the tumor site and head to a distant cancer site

CXCR3 pathway discovery

One of the most important findings beyond previous observations involves the CXCR3-CXCL10 signaling pathway. The team found that tissue therapy triggered the production of CXCL10, a chemical signal that was like a beacon for CXCR3-positive CD8+ T cells.

When researchers blocked this pathway with anti-CXCR3 antibodies, the therapeutic benefits of tissue therapy were significantly reduced. This suggests that CXCR3-CXCL10 interaction is crucial for the immune stimulation of treatment, a mechanical detail that can guide future treatment options.

The team also found that CD8-deficient mice showed a significantly reduced benefit in tissue therapy, confirming that these specific immune cells are critical for the systemic anticancer effects of treatment.

Time and durability challenges

This study reveals important limitations that can provide a basis for treatment strategies. The immune stimulation effects of tissue therapy are temporary – high oxygen levels and tumor growth inhibition will eventually decrease over time and will eventually recover.

This finding suggests that the timing of other treatments may be crucial. The window for tumors to be most vulnerable to immune attacks seems to be limited and may require carefully arranged combination therapies to maximize the benefits.

Combination therapy potential

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

The team tested the concept by combining tissue therapy with a MEK inhibitor, a MEK inhibitor that inhibits HIF1α. This combination greatly enhances the therapeutic effect compared to tissue therapy alone, demonstrating understanding of how potential mechanisms lead to improvements in treatment options.

“In addition to radiation and chemotherapy, it can help the patient’s body respond better to other types of cancer treatments, thus helping the patient’s body respond better to other types of cancer treatments,” Ganguly said.

Extend the application

While only Histototy is approved at present, this study opens the door to treating other cancer types. The ability to simultaneously destroy tumors and activate systemic immune responses is particularly valuable for patients with metastatic disease.

The technology has been expanded in Michigan and neighboring countries. As more centers adopt historians, researchers will have more opportunities to study their immune roles in a variety of patient populations and cancer types.

Future research directions

Ganguly and his team are continuing to study how tissue therapy affects the body’s response to cancer. Their work focuses on identifying which other therapies best enhance the impact of tissue photography and identifying the best timing for combination therapy.

This study has a special impact on immunotherapy approaches. Understanding how mechanical tumor damage can flood the immune system, leading to new strategies that focus on ultrasound with immune checkpoint inhibitors or other immunotherapeutic agents.

“Our work continues to understand the ways in which tissue therapy affects the entire body, which can open doors for new, potentially more effective ways to treat cancers with less side effects in patients,” Ganguly said.

With the continuous development of historical technology, this research provides a scientific basis for maximizing its therapeutic potential beyond simple tumor destruction, turning it into a tool that coordinates the body’s own defense against cancer.