scholarly journals The Promise of Immunotherapy in the Treatment of Hepatocellular Carcinoma

2017 ◽  
pp. 311-317 ◽  
Author(s):  
Anthony El-Khoueiry
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Therapy ◽  
Antitumor Immunity ◽  
Advanced Hepatocellular Carcinoma ◽  
Checkpoint Inhibition ◽  
Cell Infiltrate ◽  
Immune Mediated ◽  
Viral Therapy ◽  
Excellent Candidate ◽  
Tumor Environment

Advanced hepatocellular carcinoma (HCC) has presented a therapeutic challenge. Despite its heterogeneity, which is partially related to its various etiologies, it frequently arises in a background of chronic inflammation, which makes it a potentially excellent candidate for immunotherapeutic approaches. There is evidence of antitumor immunity in HCC as manifested by the cell infiltrate and its association with prognosis, the presence of tumor-associated antigens, and the reports of immune-mediated spontaneous regressions. However, both the liver itself and the tumor environment possess a diverse armamentarium of mechanisms that suppress antitumor immunity. Here, we describe the rationale for immunotherapy in HCC and discuss the emerging clinical data from various immunotherapeutic approaches including checkpoint inhibition, cell therapy, oncolytic viral therapy, and various combinatorial approaches. We also highlight the potential for various modalities to be adapted across different stages of the disease.

scholarly journals Sorafenib Prevents Escape from Host Immunity in Liver Cirrhosis Patients with Advanced Hepatocellular Carcinoma

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hidenari Nagai ◽  
Takanori Mukozu ◽  
Daigo Matsui ◽  
Takenori Kanekawa ◽  
Masahiro Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Liver Cirrhosis ◽  
Antitumor Immunity ◽  
Host Immunity ◽  
Th2 Cells ◽  
Host Immune System ◽  
Advanced Hepatocellular Carcinoma ◽  
Before And After ◽  
Significant Change

Purpose. It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy.Methods. Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200–800 mg/day for 4 weeks. Blood samples were collected before and after treatment.Results. Eleven patients were treated with sorafenib at 200 mg/day (200 group), 27 patients received sorafenib at 400 mg/day (400 group), and 7 patients were given sorafenib at 800 mg/day (800 group). There was no significant change in the percentage of Th1 cells after treatment in any group. However, the percentages of Th2 cells and regulatory T cells were significantly decreased after treatment in the 400 group and 800 group compared with before treatment, although there was no significant change after treatment in the 200 group.Conclusions. These results indicate that treatment with sorafenib might induce Th1 dominance and prevent the escape of tumor cells from the host immune system in LC patients with aHCC.

Current Translational and Clinical Challenges in Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 27 (29) ◽  
pp. 4789-4805 ◽  
Author(s):  
Melissa Frizziero ◽  
Mairéad G. McNamara ◽  
Angela Lamarca ◽  
Rille Pihlak ◽  
Roopa Kurup ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Therapy ◽  
Large Scale ◽  
Randomized Trials ◽  
Current Practice ◽  
Molecular Genetic ◽  
Advanced Hepatocellular Carcinoma ◽  
Checkpoint Inhibition ◽  
Advanced Hcc ◽  
Genomic Studies

Hepatocellular carcinoma (HCC) is a frequent and increasing cause of cancerrelated deaths worldwide. Reversing this trend is complicated by the varied aetiological factors leading to liver cirrhosis resulting in molecular genetic and clinical heterogeneity, combined with frequent presentation at advanced stage. Large-scale genomic studies have identified alterations in key signalling pathways for HCC development and progression, but these findings have not yet directly influenced patient management in the clinical setting. Despite these translational challenges, a small number of anti-angiogenic systemic therapy agents have succeeded in recent randomized trials enriching the repertoire of available treatments for advanced HCC. In addition, the early promise of immune checkpoint inhibition is now on the cusp of delivering changes to standard systemic therapy algorithms. This review focuses on recent translational and clinical developments that have advanced current practice and explores the challenges encountered in attempting to improve the outcomes and experience of patients diagnosed with advanced HCC.

scholarly journals Immunotherapy of HBV-related advanced hepatocellular carcinoma with short-term HBV-specific TCR expressed T cells: results of dose escalation, phase I trial

2021 ◽  
Author(s):  
Fanping Meng ◽  
Jinfang Zhao ◽  
Anthony Tanoto Tan ◽  
Wei Hu ◽  
Si-Yu Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
T Cells ◽  
T Cell ◽  
Adverse Events ◽  
Cell Therapy ◽  
Dose Escalation ◽  
Immunosuppressive Agents ◽  
Advanced Hepatocellular Carcinoma ◽  
T Cell Therapy

Abstract Background & aims Immunotherapy with hepatitis B virus (HBV)-specific TCR redirected T (HBV-TCR-T) cells in HBV-related hepatocellular carcinoma (HBV-HCC) patients after liver transplantation was reported to be safe and had potential therapeutic efficacy. We aim to investigate the safety of HBV-TCR-T-cell immunotherapy in advanced HBV-HCC patients who had not met the criteria for liver transplantation. Methods We enrolled eight patients with advanced HBV-HCC and adoptively transferred short-lived autologous T cells expressing HBV-specific TCR to perform an open-label, phase 1 dose-escalation study (NCT03899415). The primary endpoint was to evaluate the safety of HBV-TCR-T-cell therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03) during the dose-escalation process. The secondary endpoint was to assess the efficacy of HBV-TCR-T-cell therapy by evaluating the anti-tumor responses using RECIST criteria (version 1.1) and the overall survival. Results Adverse events were observed in two participants among the 8 patients enrolled. Only one patient experienced a Grade 3 liver-related adverse event after receiving a dose of 1 × 105 HBV-TCR-T cells/kg, then normalized without interventions with immunosuppressive agents. Among the patients, one achieved a partial response lasting for 27.7 months. Importantly, most of the patients exhibited a reduction or stabilization of circulating HBsAg and HBV DNA levels after HBV-TCR-T-cell infusion, indicating the on-target effects. Conclusions The adoptive transfer of HBV-TCR-T cells into advanced HBV-HCC patients were generally safe and well-tolerated. Observations of clinical efficacy support the continued development and eventual application of this treatment strategy in patients with advanced HBV-related HCC. Clinical trials registration This study was registered at ClinicalTrials.gov (NCT03899415).

scholarly journals Biomarkers and Future Perspectives for Hepatocellular Carcinoma Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuqing He ◽  
Mengyao Lu ◽  
Jing Che ◽  
Qian Chu ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antitumor Immunity ◽  
Malignant Disease ◽  
Checkpoint Inhibitors ◽  
Rapid Development ◽  
Treatment Options ◽  
Hepatocellular Cancer ◽  
Predictive Biomarkers ◽  
Basic Research ◽  
Advanced Hepatocellular Carcinoma

Hepatocellular cancer is the sixth most frequently diagnosed malignant disease worldwide, and was responsible for tens of millions of deaths in 2020; however, treatment options for patients with advanced hepatocellular carcinoma remain limited. Immunotherapy has undergone rapid development over recent years, especially in the field of immune checkpoint inhibitors (ICIs). These drugs aim to activate and enhance antitumor immunity and represent a new prospect for the treatment of patients with advanced cancer. Nevertheless, only a small proportion of liver cancer patients currently benefit from ICI-based treatment, highlighting the need to better understand how ICIs and tumors interact, as well as identify predictive biomarkers for immunotherapeutic responses. In this review, we highlight clinical trials and basic research in hepatocellular carcinoma, with a particular focus on predictive biomarkers for the therapeutic efficacy of ICIs. Predictive biomarkers for immune-related adverse events are also discussed.

AFP, AFP-L3% and DCP levels in patients with advanced hepatocellular carcinoma treated with sorafenib

2009 ◽  
Vol 47 (01) ◽  
Author(s):  
H Schulze-Bergkamen ◽  
A Weinmann ◽  
M Wörns ◽  
PR Spies ◽  
A Teufel ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Advanced Hepatocellular Carcinoma
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