Health

The liver sucks up important immune cells and disables immunotherapy. Radiation to the liver can interfere with this process-ScienceDaily

Michael Green, MD, Ph.D. Noticed that when his patient had cancer that had spread to the liver, it was less successful than when the cancer had spread to other parts of the body. Not only that, transformed immunotherapy treatment had little effect on these patients.

New research, revealing reasons and possible solutions, Nature medicineFound that liver tumors suck up important immune cells and disable immunotherapy. However, the combination of immunotherapy and radiation therapy in the liver of mice restored immune cell function with better results.

“Patients with liver metastases receive little benefit from immunotherapy, a breakthrough treatment for many cancers. Our study shows that radiation therapy can be used to reverse this resistance. This can make a real difference in the outcomes of these patients, “said Green, assistant professor of radiation oncology in Michigan medicine and the corresponding author of the paper. I will.

An interdisciplinary team at the University of Michigan Logel Cancer Center examined data from 718 patients who received immunotherapy at the center. Patients had different types of cancer that had spread to different organs such as the liver and lungs, including non-small cell lung cancer, melanoma, urothelial cancer, and renal cell carcinoma.

Repeatedly, people with liver metastases responded worse to immunotherapy. The problem wasn’t just the liver. These patients had more cancer throughout the body than similar patients whose cancer had not spread to the liver.

“The liver initiates a systemic immunosuppressive mechanism. The mechanism occurs in the liver, but it affects the whole body,” said corresponding research authors Weiping Zou, MD, Ph.D., Charles. B. de Nancrede, a professor of surgery, said. , University of Michigan Pathology, Immunology and Biology.

The liver is one of the most common sites for cancer to metastasize. It is known to interfere with the immune response in autoimmune diseases, viral infections, and organ transplants by suppressing certain important immune cells.

This was happening in metastatic cancer, as oncologists observed a lack of immune response. Green states that patients with liver metastases who received chemotherapy or targeted therapy did not show worse results than patients with other types of metastases. “It’s unique to immunotherapy,” he says.

Looking within the microenvironment of liver metastases, researchers saw the tumor sucking up T cells, the immune cells that should be working to attack the cancer. Not only were T cells eliminated in the liver, which created an immune desert throughout the body. As a result, it was unable to activate the immune system and fight tumors in any area.

Researchers used mice with liver metastases to give radiation therapy directly to liver tumors. This stopped T cell death. Upon recovery of T cells, immune checkpoint inhibitors were able to activate the immune system and eliminate systemic cancers, similar to the results seen in non-liver metastases.

“It is always a challenge to identify new mechanisms of immunosuppression and find ways to address them. With these promising results, we are now starting clinical trials in this area to better improve the mechanism in human tumors. I aim to understand it well, “says Green.

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material Provided by University of Michigan-University of Michigan.. Original written by Nicole Fawcett. Note: The content can be edited in style and length.

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