In a new study, researchers found when patients had cancer that spread to the liver, they fared much more poorly than when cancer spread to other parts of the body.
In addition, patients with liver metastases receive little benefit from immunotherapy, a treatment that has been a game-changer for many cancers.
They found that this is because tumors in the liver siphon off critical immune cells, rendering immunotherapy ineffective.
Coupling immunotherapy with radiotherapy to the liver could restore the immune cell function and lead to better outcomes.
The research was conducted by a team at Michigan Medicine.
In the study, the team looked at data from 718 patients who had received immunotherapy at the center.
Patients had a variety of cancer types, including non-small cell lung cancer, melanoma, urothelial cancer, and renal cell cancer, which had spread to different organs, including the liver and lungs.
Repeatedly, those with liver metastases had worse responses to immunotherapy.
The issue was not just in the liver either: these patients had more cancer throughout their bodies, compared to similar patients whose cancer had spread but not to the liver.
The liver is one of the most common sites to which cancer metastasizes.
It’s known to interfere with the immune response in autoimmune diseases, viral infections, and organ transplants by suppressing certain critical immune cells.
This was playing out in metastatic cancer as oncologists observed a lack of immune response.
The team notes that patients with liver metastases who received chemotherapy or targeted therapies did not have worse outcomes compared to those with other types of metastases.
Looking within the microenvironment of the liver metastases, the researchers saw that the tumors were siphoning off the T cells – immune cells that should have been working to attack cancer.
Not only were the T cells being eliminated in the liver, but this was also creating an immune desert throughout the body. As a result, the immune system could not be activated to fight tumors at any sites.
Using mice with liver metastases, the researchers delivered radiation therapy directly to the tumors in the liver. This stopped T cell death.
With the T cells restored, an immune checkpoint inhibitor was then able to activate the immune system to eliminate cancer throughout the body, on par with results seen in non-liver metastases.
Clinical trials are currently being developed.
One author of the study is Michael Green, M.D., Ph.D.
The study is published in Nature Medicine.
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