Liver Cancer Immunity.

Abstract

Primary liver cancer has an increasing incidence and poor patient outcomes. Potentially curative options such as surgical resection or liver transplantation are limited to the subset of patients with early-stage disease. The available systemic treatment options have limited efficacy. Immuno-oncology has revolutionized cancer treatment across a variety of malignancies, although durable responses occur in a minority of patients. Immune-based approaches have garnered significant interest in both hepatocellular carcinoma and cholangiocarcinoma given the etiologic association of these malignancies with inflammation. The liver cancer tumor immune microenvironment is complex with diverse populations of innate and adaptive immune cells that impact cancer immune evasion, response to immunotherapy, and patient survival. Although the response rate to immune checkpoint inhibitor monotherapy has been relatively disappointing in liver cancer, emerging combination immunotherapeutic approaches have shown promise. Herein, we review the immune ecosystem of human liver cancer as well as current and emerging combination immunotherapeutic regimens harnessing immune checkpoint inhibition with molecularly targeted therapy, locoregional therapy, and immune microenvironment targeted therapy.