How Compatible Are Immune Checkpoint Inhibitors and Thermal Ablation for Liver Metastases?

SIMPLE SUMMARY: Although immune checkpoint inhibitors (ICIs) have achieved great progression in cancer treatment, the efficacy of ICI monotherapy is still limited. Meanwhile, the negative efficacy of thermal ablation for liver metastases is the high rate of local tumor progression. Since thermal ablation-induced inflammation and increases in tumor antigens have been suggested to promote the cancer-immunity cycle, thermal ablation and ICI can boost the immune response against cancer cells as one of the positive synergy effects. The findings of preclinical and clinical research have provided supportive evidence for the combination of ICIs with thermal ablation reversing T-cell exhaustion and demonstrating synergy. However, the clinical feasibility of immune response activation by combination therapy with ICI monotherapy and thermal ablation appears to be limited, it may be not very common phenomena. ABSTRACT: Cancer immunotherapy, which reactivates the weakened immune cells of cancer patients, has achieved great success, and several immune checkpoint inhibitors (ICIs) are now available in clinical practice. Despite promising clinical outcomes, favorable responses are only observed in a fraction of patients, and resistance mechanisms, including the absence of tumor antigens, have been reported. Thermal ablation involves the induction of irreversible damage to cancer cells by localized heat and may result in the release of tumor antigens. The combination of immunotherapy and thermal ablation is an emerging therapeutic option with enhanced efficacy. Since thermal ablation-induced inflammation and increases in tumor antigens have been suggested to promote the cancer-immunity cycle, the combination of immuno-oncology (IO) therapy and thermal ablation may be mutually beneficial. In preclinical and clinical studies, the combination of ICI and thermal ablation significantly inhibited tumor growth, and synergistic antitumor effects appeared to prolong the survival of patients with secondary liver cancer. However, evidence for the efficacy of ICI monotherapy combined with thermal ablation is currently insufficient. Therefore, the clinical feasibility of immune response activation by ICI monotherapy combined with thermal ablation may be limited, and thermal ablation may be more compatible with dual ICIs (the IO–IO combination) to induce strong immune responses.