Immunotherapy for hepatocellular carcinoma: Current and future

Abstract

Hepatocellular carcinoma (HCC) arises on the background of chronic liver disease. Despite the development of effective anti-viral therapeutics HCC is continuing to rise, in part driven by the epidemic of non-alcoholic fatty liver disease. Many patients present with advanced disease out with the criteria for transplant, resection or even locoregional therapy. Currently available therapeutics for HCC are effective in a small minority of individuals. However, there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers, great opportunities now exist for treating HCC with newer and more sophisticated agents. Whilst checkpoint inhibitors are at the forefront of this revolution, other therapeutics such as inhibitory cytokine blockade, oncolytic viruses, adoptive cellular therapies and vaccines are emerging. Broadly these may be categorized as either boosting existing immune response or stimulating de novo immune response. Although some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy, either in combination with one another or in combination with treatment modalities such as locoregional therapy. Together these agents are likely to generate new and exciting opportunities for treating HCC, which are summarized in this review.

Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer

“…Most studies on ex vivo DC vaccines employ a similar procedure: first, mononuclear cells are isolated from peripheral blood and transferred into cell culture. Then, DCs are stimulated with activating cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4 and TNF-α and the exposure to a specific antigen is induced, usually by incubation with either tumor lysates or TAAs, but methods of cell fusion or tumor-associated RNA or DNA transfection have also been described [ 129 , 145 ]. Subsequently, the activated DCs are transferred to the patient where the injection of mature, antigen-loaded DCs results in the induction of both CD8+ cytotoxic T cells and CD4+ Th cells, particularly IFN-γ-producing Th1 cells [ 129 , 146 ].…”

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

“…ICI therapy was recently approved as second-line therapy for HCC (Table 1) (7,9). Other promising immunotherapies are in development and are aimed at boosting existing or de novo immune responses, including vaccines and oncolytic viruses, and combination ICI therapy (167). Anticipation awaits the results of NCT03298451, a phase 3 clinical trial assessing anti-PD-L1 and anti-CTLA-4 combination therapy vs. monotherapy as better first-line options than sorafenib [HIMALAYA trial, (NCT03298451)].…”

RNA N6-Methyladenosine-Related Gene Contribute to Clinical Prognostic Impact on Patients With Liver Cancer

“…Immune checkpoint proteins including the programmed cell death protein 1 (PD-1/PDCD1), programmed death-ligand-1 (PD-L1/CD274), and cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) are established prognostic markers for LC patients (Cariani and Missale, 2019;El Dika et al, 2019;Johnston and Khakoo, 2019). Recent studies showed that tumor mutation burden (TMB) is also significantly associated with the susceptibility to anti-tumor immunotherapy, and a higher TMB indicates better prognosis in many cancer types (Peng et al, 2019;Wang and Li, 2019).…”