Adding immunotherapy to ablation may benefit colorectal cancer patients with liver metastasis

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A study has found that radiofrequency ablation to treat liver metastases in patients with colorectal cancer, induces antitumour immune responses in human samples of primary colon tumour.

Also, mice treated with a combination of radiofrequency ablation and an immune checkpoint inhibitor survived longer than those treated with either one of the two therapies, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

“Liver is the most common site of colorectal cancer metastasis, and about 20% of colorectal cancer patients have liver metastases at the time of diagnosis [synchronous liver metastases],” said Binfeng Lu an associate professor in the Department of Immunology at the University of Pittsburgh.

Resection of liver metastases first (liver-first approach) is considered the best option for patients whose hepatic disease is predominant and if the primary tumour is asymptomatic or if symptoms are easy to manage, Lu explained. For some patients, radiofrequency ablation of the liver metastases is recommended as an alternative to surgery of the liver metastases, especially if the liver nodules are small.

“Radiofrequency ablation is mainly recommended as local treatment for its physical effect of tumour destruction presently, and its immune effect has not been well studied. Our study revealed that radiofrequency ablation elicits systemic antitumour responses, and combining this with immune checkpoint blockade can potentially unleash the powerful immunotherapeutic effect of radiofrequency ablation,” Lu said.

Lu and his team, in collaboration with researchers from Soochow University in China, analysed colorectal tumour samples collected from 78 patients with liver metastases admitted to the Third Affiliated Hospital of Soochow University. Of these patients, 38 received radiofrequency ablation of liver metastases before their primary colorectal tumours were treated.

The researchers found that ablation of liver metastases increased the infiltration of T cells in the primary colon tumour, and that it also increased levels of the immune-inhibitory molecule PD-L1 in tumour cells and immune cells within the tumour.

“These studies show that liver radiofrequency ablation results in systematic inflammatory responses in the primary colon tumours and makes them more accessible to T cells. These properties of radiofrequency ablation suggest that it can potentially be used to make colorectal cancer patients who are nonresponsive to PD-1-based immunotherapy become responsive,” Lu said.

The researchers then conducted experiments in mice and found that an anti-PD-1 antibody was effective in inhibiting the radiofrequency ablation-induced PD-L1 upregulation, and a combination of radiofrequency ablation and PD-1 blockade was more potent than either ablation or PD-1 blockade tested individually.

“These studies suggest that radiofrequency ablation complements and synergises with anti-PD-1 immunotherapy,” Lu said. “As immune checkpoint inhibitors become available to colorectal cancer patients in the clinic, radiofrequency ablation might be used as adjuvant immunotherapy in patients with multiple metastases.”

The investigators are planning to initiate a phase I clinical trial to evaluate the efficacy of combination therapy with radiofrequency ablation and anti-PD-1 antibody for patients with liver metastases from colorectal cancer.