Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy

Abstract

Hepatitis B virus (HBV) infection is the main risk factor for the development of hepatocellular carcinoma (HCC), the most common type of liver cancer, with high incidence and mortality worldwide. Surgery, liver transplantation, and ablation therapies have been used to treat early HBV-caused HCC (HBV-HCC); meanwhile, in the advanced stage, chemoradiotherapy and drug-targeted therapy are regularly considered, but with limited efficacy. Recently, immunotherapies, such as tumor vaccine therapy, adoptive cell transfer therapy, and immune checkpoint inhibitor therapy, have demonstrated promising efficacy in cancer treatment. In particular, immune checkpoint inhibitors can successfully prevent tumors from achieving immune escape and promote an anti-tumor response, thereby boosting the therapeutic effect in HBV-HCC. However, the advantages of immune checkpoint inhibitors in the treatment of HBV-HCC remain to be exploited. Here, we describe the basic characteristics and development of HBV-HCC and introduce current treatment strategies for HBV-HCC. Of note, we review the principles of immune checkpoint molecules, such as programmed cell death protein 1(PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in HBV-HCC, as well as related inhibitors being considered in the clinic. We also discuss the benefits of immune checkpoint inhibitors in the treatment of HBV-HCC and the efficacy of those inhibitors in HCC with various etiologies, aiming to provide insights into the use of immune checkpoint inhibitors for the treatment of HBV-HCC.

Hepatic arterial infusion chemotherapy combined with lenvatinib and PD‐1 inhibitors versus lenvatinib and PD‐1 inhibitors for HCC refractory to TACE

“…Inhibition of the activity of immunological checkpoint molecules can prevent the negative HAIC-Len-PD1 in TACE-refractory HCC regulation of the immune response, enhance the capacity of immune cells to eradicate tumor cells, and control the growth of malignancies. 36 Additionally, immunity activation was further enhanced in triple combination therapy, thus providing more benefits for HBsAg-positive individuals. Subgroup analyses of OS demonstrated that patients who had just two sessions of TACE could benefit more from the triple therapy than those with over two procedures of TACE.…”

“…In addition, HBsAg‐positive patients benefited more from tri‐combination treatment while HBsAg‐negative patients were less sensitive to tri‐combination therapy. Inhibition of the activity of immunological checkpoint molecules can prevent the negative regulation of the immune response, enhance the capacity of immune cells to eradicate tumor cells, and control the growth of malignancies 36 . Additionally, immunity activation was further enhanced in triple combination therapy, thus providing more benefits for HBsAg‐positive individuals.…”

The evolution of lung adenocarcinoma precursors is associated with chromosomal instability and transition from innate to adaptive immune response/evasion

“…Alternatively, an immunebased strategy may be more widely applicable, as immune evasion is a universal phenomenon in cancers. Immune prevention has shown success in cancers associated with infectious agents such as hepatitis B 47 and human papillomavirus 48 . However, applying lung cancer immune prevention faces challenges due to our limited understanding of the evolving interplay between premalignant/malignant cells and the host's anti-tumor immunity during the formation and progression of pre-cancerous lesions.…”

Liver Transplantation for Hepatocellular Carcinoma beyond the Milan Criteria: A Specific Role for Living Donor Liver Transplantation after Neoadjuvant Therapy

“…Bridging procedures such as transcatheter arterial chemoembolization and selective internal radiotherapy have been able to further improve oncological outcomes in patients with HCC, and new therapeutic approaches such as immunotherapy have been established [ 5 , 6 , 7 , 8 , 9 , 10 ]. Even if immune checkpoint inhibition is currently not implemented in the bridging of patients with HCC on the waiting list, it is encouraging that this approach has the potential to further improve bridging therapy in combination with conventional bridging methods [ 8 , 11 , 12 , 13 ].…”