Management and Treatment of Hepatocellular Carcinoma with Immunotherapy: A Review of Current and Future Options

Abstract

With mortality rates of liver cancer doubling in the last 20 years, this disease is on the rise and has become the fifth most common cancer in men and the seventh most common cancer in women. Hepatocellular carcinoma (HCC) represents approximately 90% of all primary liver cancers and is a major global health concern. Patients with HCC can be managed curatively with surgical resection or with liver transplantation, if they are diagnosed at an early stage. Unfortunately, most patients with HCC present with advanced stages of the disease and have underlying liver dysfunction, which allows only 15% of patients to be eligible for curative treatment. Several different treatment modalities are available, including locoregional therapy radiofrequency ablation, microwave ablation, percutaneous ethanol injection, trans-arterial chemoembolization, transarterial radio-embolization, cryoablation, radiation therapy, stereotactic radiotherapy, systemic chemotherapy, molecularly targeted therapies, and immunotherapy. Immunotherapy has recently become a promising method for inhibiting HCC tumor progression, recurrence, and metastasis. The term "Immunotherapy" is a catch-all, encompassing a wide range of applications and targets, including HCC vaccines, adoptive cell therapy, immune checkpoint inhibitors, and use of oncolytic viruses to treat HCC. Immunotherapy in HCC is a relatively safe option for treating patients with advanced disease in the USA who are either unable to receive or failed sorafenib/lenvatinib therapy and thus may offer an additional survival benefit for these patients. The purpose of this review is to elaborate on some of the most recent advancements in immunotherapy.

Synthesis of Poly(Malic Acid) Derivatives End-Functionalized with Peptides and Preparation of Biocompatible Nanoparticles to Target Hepatoma Cells

“…For amphiphilic block copolymers, the molar mass of the PMLABe block was calculated using the integration of the methylene protons of the PEG block (δ = 3.59 ppm, Figure 4 B and Figure S1 ), whose molar mass was given by the supplier, and the integration of the methylene protons of the PMLABe block (δ = 5.14 ppm, Figure 4 B and Figure S1 ). As shown by results gathered in Table 3 , calculated molar masses of PMLABe block were in good agreement with the theoretical ones fixed by the monomer/initiator ratio, thus highlighting the quite good control of the polymerization reaction [ 30 ].…”

“…The advanced stages of hepatocellular carcinoma (HCC), the major primary liver cancer, still have a very poor prognosis despite the recent progress in the therapeutic management of this cancer [ 29 ]. In addition, only a few patients are eligible for curative treatments in the early stages of the disease, or can be treated downstream to decrease the stage of their tumor so that they may be eligible for curative treatments [ 30 , 31 ]. Consequently, there is an urgent need for tools allowing effective therapies and/or early diagnosis of HCC.…”

Transarterial embolization modulates the immune response within target and non-target hepatocellular carcinomas

“…These dismal statistics issue, at least in part, from the fact that there remain limited therapeutic options for patients with HCC. Given the potential for locoregional therapies to engage the immune system, and the well documented connection between patient outcomes and immune response, many clinical trials are already underway which are designed to test the presumed benefit of combination locoregional and immunotherapy 44 ; however, there remains a paucity of data characterizing the influence of embolotherapy on the immune landscape that is required to inform these trials.…”

Immunmodulatory Treatment Strategies of Hepatocellular Carcinoma: From Checkpoint Inhibitors Now to an Integrated Approach in the Future

“… The most important immune checkpoints. Based on [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Abbreviations: APC, antigen-presenting cell; CTLA-4, cytotoxic T lymphocyte protein 4; LAG-3, lymphocyte activation gene 3 protein; PD1, programmed cell death protein 1; PDL1/2, programmed cell death protein ligand 1/2; TIGIT, T cell immunoreceptor with immunoglobulin and ITIM domains; TIM-3, T cell immunoglobulin and mucin-domain containing.…”

“…In the context of human cancer therapy, the currently most studied ICIs are PD1 (programmed cell death protein 1), CTLA-4 (cytotoxic T lymphocyte protein 4), LAG-3 (lymphocyte activation gene 3 protein), and, TIM-3 (T cell immunoglobulin and mucin-domain containing)-for an overview including the respective ligands, see also Figure 2. [16][17][18][19][20][21][22]. Abbreviations: APC, antigen-presenting cell;…”