When cancer spreads to the liver: Finding a way around this dangerous complication

Liver metastasis is a dangerous complication in any cancer, and it leads to very poor prognosis for cancer patients. But experts may have a way to overcome this.

One danger that all cancer patients face is liver metastasis. In laymen terms, this means that the cancer has spread to the liver. This is a dangerous complication and, most of the time, it is irreversible, and it significantly increases the mortality rate of cancer patients. However, researchers have been trying a way to overcome this complication by understanding the reason for poor prognosis and developing new treatment procedure. Now, a new study finds that tumors in the liver siphon off critical immune cells, rendering immunotherapy ineffective. But coupling immunotherapy with radiotherapy to the liver may restore the immune cell function and led to better outcomes. This has tremendous implications and may well pave the way for better treatment and prognosis for patients. The study is published in Nature Medicine.

Immunotherapy vs radiation therapy

According to researchers from University of Michigan Rogel Cancer Center, patients with liver metastases receive little benefit from immunotherapy, a treatment that has been a game-changer for many cancers. This research suggests that radiation therapy can reverse this resistance. This has potential to make a real difference in outcomes for these patients. A multidisciplinary team from the University 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.

Liver metastasis suppresses immune response

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 initiates a systemic immunosuppressive mechanism. The mechanism happens in the liver, but the entire body suffers the systemic impact.

The liver is one of the most common site to which cancer metastasizes. It's known to interfere with immune response in autoimmune diseases, viral infections and organ transplants by suppressing certain critical immune cells. This plays out in metastatic cancer as oncologists observed a lack of immune response. Patients with liver metastases who received chemotherapy or targeted therapies did not have worse outcomes compared to those with other types of metastases. It's unique to immunotherapy.

Tumous in liver siphon off the T cells

Looking within the microenvironment of the liver metastases, researchers saw that the tumors were siphoning off the T cells -- immune cells that should have been working to attack the 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.

Activating the immune system with radiation therapy

Using mice with liver metastases, 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 the cancer throughout the body, on par with results seen in non-liver metastases.