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Adding Immunotherapy to Radiofrequency Ablation in Colorectal Cancer With Liver Metastasis Shows Promise in Preclinical Models

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Key Points

  • Researchers analyzed colorectal tumor samples collected from 78 patients with liver metastases, and 38 received radiofrequency ablation of liver metastases before their primary colorectal tumors were treated.
  • Researchers found that radiofrequency ablation of liver metastases increased the infiltration of T cells in the primary colon tumor, and that it also increased levels of the immune-inhibitory molecule PD-L1 in tumor cells and immune cells within the tumor.
  • In mice, 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 radiofrequency ablation or PD-1 blockade tested individually.

In a retrospective case-controlled study conducted in patients with colorectal cancer who had received primary tumor resection with or without preoperative radiofrequency ablation for liver metastases, the electrical procedure was found to induce antitumor immune responses in the colorectal tumor samples, as reported by Shi et al in Clinical Cancer Research. These investigators also found that mice treated with a combination of radiofrequency ablation and an immune checkpoint inhibitor survived longer than those treated with either of the two therapies.

“[The] 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, PhD, 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 tumor is asymptomatic or if symptoms are easy to manage, Dr. Lu explained. For these patients, radiofrequency ablation, a procedure that uses electrical energy to destroy cancer cells, 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 tumor destruction presently, and its immune effect has not been well studied. Our study revealed that [radiofrequency ablation] elicits systemic antitumor responses, and combining this with immune checkpoint blockade can potentially unleash the powerful immunotherapeutic effect of [radiofrequency ablation],” Dr. Lu said.

Study Findings

Dr. Lu and his team, in collaboration with researchers from Soochow University in China, analyzed colorectal tumor 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 tumors were treated.

The researchers found that radiofrequency ablation of liver metastases increased the infiltration of T cells in the primary colon tumor, and that it also increased levels of the immune-inhibitory molecule programmed cell death ligand 1 [PD-L1] in tumor cells and immune cells within the tumor.

“These studies show that liver [radiofrequency ablation] results in systematic inflammatory responses in the primary colon tumors and makes them more accessible to T cells. These properties of [radiofrequency ablation] suggest it can potentially be used to make colorectal cancer patients who are nonresponsive to [programmed cell death protein 1 (PD-1)]–based immunotherapy become responsive,” Dr. 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 radiofrequency ablation or PD-1 blockade tested individually.

“These studies suggest that [radiofrequency ablation] complements and synergizes with anti–PD-1 immunotherapy,” Dr. 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 concluded: “The PD-L1–PD-1 axis plays a critical role in dampening [radiofrequency ablation]–induced antitumor immune responses, and this study provides a strong rationale for combining [radiofrequency ablation] and the PD-L1/PD-1 blockade in the clinical setting.” They 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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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