Current status and perspectives of immune-based therapies for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a frequent cancer with a high mortality. For early stage cancer there are potentially curative treatments including local ablation, resection and liver transplantation. However, for more advanced stage disease, there is no optimal treatment available. Even in the case of a "curative" treatment, recurrence or development of a new cancer in the precancerous liver is common. Thus, there is an urgent need for novel and effective (adjuvant) therapies to treat HCC and to prevent recurrence after local treatment in patients with HCC. The unique immune response in the liver favors tolerance, which remains a genuine challenge for conventional immunotherapy in patients with HCC. However, even in this "immunotolerant" organ, spontaneous immune responses against tumor antigens have been detected, although they are insufficient to achieve significant tumor death. Local ablation therapy leads to immunogenic tumor cell death by inducing the release of massive amounts of antigens, which enhances spontaneous immune response. New immune therapies such as dendritic cell vaccination and immune checkpoint inhibition are under investigation. Immunotherapy for cancer has made huge progress in the last few years and clinical trials examining the use of immunotherapy to treat hepatocellular carcinoma have shown some success. In this review, we discuss the current status of and offer some perspectives on immunotherapy for hepatocellular carcinoma, which could change disease progression in the near future.

Keywords: Dendritic cell vaccination; Dendritic cells; Hepatocellular carcinoma; Immunotherapy; Therapy.

Figure 1

Immune-based therapies for hepatocellular carcinoma. Tumor-specific T cells can be stimulated by several ways including adoptive cell therapy, tumor vaccines, cytokines or by inhibiting immune suppressive mechanisms (immune checkpoint inhibitors, depletion of Tregs or MDSCs). These tumor-specific T cells are able to kill the tumor cells in an antigen-specific way. Conventional therapies (RFA, TACE, PEI, microwave ablation, TARE) can destroy tumor cells, which result in the release of tumor antigens and danger-associated molecular patterns that can activate DCs resulting in the activation of tumor-specific T cells. RFA: Radiofrequency ablation; PEI: Percutaneous ethanol injection; TACE: Transarterial chemoembolization; TARE: Transarterial radioembolization; DAMPs: Danger-associated molecular patterns; PAMPs: Pathogen-associated molecular patterns; DC: Dendritic cell; NK: Natural killer; LAK: Lymphokine-activated killer; NKT cell: Natural killer T cell; CIK: Cytokine-induced killer; CAR: Chimeric antigen receptor; CTL: Cytotoxic T lymphocyte; Treg: Regulatory T cell; MDSC: Myeloid derived suppressor cells; CTLA-4: Cytotoxic T lymphocyte antigen 4; PD-1: Programmed-death 1.