Abstract
Liver cancer is the third leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Liver resection or transplantation offer the only potentially curative options for HCC; however, many patients are not candidates for surgical resection, either due to presentation at advanced stages or poor liver function and portal hypertension. Liver transplantation is also limited to patients with certain characteristics, such as those that meet the Milan criteria (one tumor ≤ 5 cm, or up to three tumors no larger than 3 cm, along with the absence of gross vascular invasion or extrahepatic spread). Locoregional therapies, such as ablation (radiofrequency, ethanol, cryoablation, microwave), trans-arterial therapies like chemoembolization (TACE) or radioembolization (TARE), and external beam radiation therapy, have been used mainly as palliative measures with poor prognosis. Therefore, emerging novel systemic treatments, such as immunotherapy, have increasingly become popular. HCC is immunogenic, containing infiltrating tumor-specific T-cell lymphocytes and other immune cells. Immunotherapy may provide a more effective and discriminatory targeting of tumor cells through induction of a tumor-specific immune response in cancer cells and can improve post-surgical recurrence-free survival in HCC. We herein review evidence supporting different immunomodulating cell-based technology relative to cancer therapy in vaccines and targeted therapies, such as immune checkpoint inhibitors, in the management of hepatocellular carcinoma among patients with advanced disease.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, which originates from hepatocytes [1,2]
Fibrosis of the liver stemming from chronic alcohol abuse, metabolic liver disease, exposure to aspergillus fungal aflatoxin, Clonorchis sinensis infection, exposure to polyvinyl chloride, and exposure to other environmental toxins such as biphenyls, trichloroethylene, and carbon tetrachloride has been associated with HCC development [1,2,3]
The crosstalk between Tumor-Associated Macrophages (TAMs) and other cell types such as Myeloid-Derived Suppressor Cells (MDSCs) and Tregs generates a series of changes in chemokine production, MHCI/II expression, and downstream T cell activation, which are correlated with immunosuppression and HCC development [13]
Summary
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, which originates from hepatocytes [1,2]. Surgical resection and organ transplantation remain the only potentially curative options for management of hepatocellular carcinoma [4]. In view of inflammatory-based pathogenesis, there has been a growing interest in the application of immunotherapy as a systemic therapy in management of patients with HCC. Despite recent advances in the management of hepatobiliary malignancies, the incidence of HCC continues to rise globally with increased mortality in advanced stages [5,6]. We review the role of immunomodulating cell-based technology in the development of vaccines, as well as immune checkpoint inhibitors administered in the management of patients with hepatocellular carcinoma
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