Eliciting a Systemic Immune Response against Liver Tumors Utilizing Locoregional Therapies - A Systematic Review of Prospective Studies

Abstract

Introduction: While surgical resection remains the gold standard for liver tumors, they are increasingly being treated with locoregional therapies such as ablation or irradiation, often in combination with immunotherapy. This combination may be effective for tumors not directly targeted, which is known as the abscopal effect. We set out to review the literature for prospective studies evaluating the potential of liver directed locoregional therapy to elicit a systemic immune response against metastatic cancers. Methods: Four databases were systematically searched to identify prospective studies evaluating an immune response to ablation, embolization, or irradiation of liver tumors. We included prospective studies measuring an increase in immune cells in the blood or tumor microenvironment or an enhancement of the effect of immunotherapy following locoregional therapy. Colorectal liver metastases (CRCLM), lung cancer and melanoma as well as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma were included. Results: Two reviewers screened 3651 articles independently. We identified 3 prospective studies evaluating CRCLM, 9 prospective studies evaluating HCC, 2 studies evaluating Cholangiocarcinoma, and 4 studies evaluating other cancers. While loco-regional therapies for HCC, cholangiocarcinoma, melanoma, and lung metastases elicited a significant immune response and improved patients’ survival when combined with immunotherapy, a similar benefit was not identified in CRCLM. Conclusions: Locoregional therapies may elicit a significant systemic anti-tumoral immune response against several types of liver cancers but are less beneficial to patients with CRCLM. Methods to modify the immunosuppressive microenvironment of CRCLM should be investigated to potentiate an effective immune response against metastatic colorectal cancer.