Immunotherapy with radiotherapy could improve outcomes of cancers in liver

In a new study, researchers have revealed why patients with cancer that spreads to the liver fare poorly when compared with patients whose cancer spreads to other parts of the body. The study was conducted at the University of Michigan, US. 

The team found that tumours in the liver siphon off critical immune cells, rendering immunotherapy ineffective. However, they revealed that coupling immunotherapy with radiotherapy to the livers of mice restored the immune cell function and led to better outcomes.

“Patients with liver metastases receive little benefit from immunotherapy, a treatment that has been a game-changer for many cancers. Our research suggests that we can reverse this resistance using radiation therapy. This has potential to make a real difference in outcomes for these patients,” said Dr Michael Green, corresponding author on the paper.

The team looked at data from 718 patients who had received immunotherapy. 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 initiating a systemic immunosuppressive mechanism. The mechanism happens in the liver, but we see the systemic impact throughout the body,” said corresponding study author Dr Weiping Zou.

Green noted that 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.”

Investigating the microenvironment of the liver metastases, the researchers saw that the tumours were siphoning off T cells. 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 tumours at any sites.

Using mice with liver metastases, researchers delivered radiation therapy directly to the tumours in the liver. This prevented 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.

“It is always a challenge to identify a novel mechanism of immune suppression and find a way to address it. With these promising results, we are now looking to open clinical trials in this space to better understand the mechanisms at play in human tumours,” Green said.

The study was published in Nature Medicine.