An international team of researchers found that preoperative radiofrequency ablation (RFA) helped to induce anti-tumor immune responses in patients with primary colon tumors with liver metastasis.
The study, titled “PD-1 Blockade Boosts Radiofrequency Ablation–Elicited Adaptive Immune Responses against Tumor” and published in the Clinical Cancer Research journal, was conducted by scientists at the University of Pittsburgh, Pennsylvania, working with several Chinese institutions.
Colorectal cancer involves the growth of tumors in certain parts of the large intestine (colon/rectum). When cancer cells spread to different areas through the blood or lymphatic system, they can form new tumors in other organs, particularly the liver. “Liver is the most common site of colorectal cancer metastasis, and about 20 percent of colorectal cancer patients have liver metastases at the time of diagnosis [synchronous liver metastases],” Binfeng Lu, PhD, an associate professor in the Department of Immunology at the University of Pittsburgh, said in a press release.
When colorectal cancer with liver metastasis is identified, the best alternative therapeutic option to surgery is RFA. This procedure utilizes heat induced from alternating current electrical energy to destroy tumor cells. Like surgery, however, RFA is known to have little effect in preventing cancer progression, and, as such, researchers investigated the mechanisms and limitations of RFA.
“RFA is mainly recommended as a local treatment for its physical effect of tumor destruction presently, and its immune effect has not been well studied. Our study revealed that RFA elicits systemic antitumor responses, and combining this with immune checkpoint blockade can potentially unleash the powerful immunotherapeutic effect of RFA,” Dr. Lu said.
The team examined tumor samples from 78 colorectal cancer patients with liver metastases. Among the patients, 38 were treated with RFA for liver metastases prior to treatment of their primary colorectal tumors. Results suggested that RFA boosts the presence of immune white cells (T cells) and the expression of an immune-inhibitory protein named PD-L1 in both primary colon tumor cells and immune cells within the tumor microenvironment. Experiments conducted in a mice model further revealed that the use of an anti-PD-1 antibody inhibited RFA induced PD-L1, and a combination of RFA and PD-1 blockade was more potent than RFA or PD-1 blockade alone.
“These studies show that liver RFA results in systematic inflammatory responses in the primary colon tumors and makes them more accessible to T cells. These properties of RFA suggest it can potentially be used to make colorectal cancer patients who are nonresponsive to PD-1-based immunotherapy become responsive,” Dr. Lu said. “RFA complements and synergizes with anti-PD-1 immunotherapy. As immune checkpoint inhibitors become available to colorectal cancer patients in the clinic, RFA might be used as adjuvant immunotherapy in patients with multiple metastases.”
In the near future, researchers plan a Phase 1 clinical trial to study the efficiency of a combination treatment of RFA and anti-PD-1 antibody in colorectal cancer patients with liver metastases.