Roles of the Immune System in the Development and Progression of Hepatocellular Carcinoma

Liver Cancers ◽  
2018 ◽  
pp. 23-37
Author(s):  
João Maurício ◽  
Helen Reeves ◽  
Caroline L. Wilson
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System

The interplay between gut microbiota and the immune system in liver transplant recipients and its role in infections

2021 ◽  
Author(s):  
Giuseppe Ancona ◽  
Laura Alagna ◽  
Andrea Lombardi ◽  
Emanuele Palomba ◽  
Valeria Castelli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Liver Transplant ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Transplant Recipients ◽  
Liver Transplant Recipients

Liver transplantation (LT) is a life-saving strategy for patients with end-stage liver disease, hepatocellular carcinoma and acute liver failure. LT success can be hampered by several short-term and long-term complications. Among them, bacterial infections, especially due to multidrug-resistant germs, are particularly frequent with a prevalence between 19 and 33% in the first 100 days after transplantation. In the last decades, a number of studies have highlighted how gut microbiota (GM) is involved in several essential functions to ensure the intestinal homeostasis, becoming one of the most important virtual metabolic organs. GM works through different axes with other organs, and the gut-liver axis is among the most relevant and investigated ones. Any alteration or disruption of GM is defined as dysbiosis. Peculiar phenotypes of GM dysbiosis have been associated to several liver conditions and complications, such as chronic hepatitis, fatty liver disease, cirrhosis and hepatocellular carcinoma. Moreover, there is growing evidence of the crucial role of GM in shaping the immune response, both locally and systemically, against pathogens. This paves the way to the manipulation of GM as a therapeutic instrument to modulate the infectious risk and outcome. In this minireview we provide an overview of the current understanding on the interplay between gut microbiota and the immune system in liver transplant recipients and the role of the former in infections.

The role of the immune system in the control of hepatocellular carcinoma

2004 ◽  
Vol 16 (12) ◽  
pp. 1257-1260 ◽  
Author(s):  
James P O'Beirne ◽  
Phillip M Harrison
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System

scholarly journals The Epigenetic Modulation of Cancer and Immune Pathways in Hepatitis B Virus-Associated Hepatocellular Carcinoma: The Influence of HBx and miRNA Dysregulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Kurt Sartorius ◽  
Ping An ◽  
Cheryl Winkler ◽  
Anil Chuturgoon ◽  
Xiaodong Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Host Genome ◽  
Epigenetic Changes ◽  
Epigenetic Change ◽  
Genome Expression ◽  
B Virus

Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) pathogenesis is fueled by persistent HBV infection that stealthily maintains a delicate balance between viral replication and evasion of the host immune system. HBV is remarkably adept at using a combination of both its own, as well as host machinery to ensure its own replication and survival. A key tool in its arsenal, is the HBx protein which can manipulate the epigenetic landscape to decrease its own viral load and enhance persistence, as well as manage host genome epigenetic responses to the presence of viral infection. The HBx protein can initiate epigenetic modifications to dysregulate miRNA expression which, in turn, can regulate downstream epigenetic changes in HBV-HCC pathogenesis. We attempt to link the HBx and miRNA induced epigenetic modulations that influence both the HBV and host genome expression in HBV-HCC pathogenesis. In particular, the review investigates the interplay between CHB infection, the silencing role of miRNA, epigenetic change, immune system expression and HBV-HCC pathogenesis. The review demonstrates exactly how HBx-dysregulated miRNA in HBV-HCC pathogenesis influence and are influenced by epigenetic changes to modulate both viral and host genome expression. In particular, the review identifies a specific subset of HBx induced epigenetic miRNA pathways in HBV-HCC pathogenesis demonstrating the complex interplay between HBV infection, epigenetic change, disease and immune response. The wide-ranging influence of epigenetic change and miRNA modulation offers considerable potential as a therapeutic option in HBV-HCC.

scholarly journals Lymphocyte Landscape after Chronic Hepatitis C Virus (HCV) Cure: The New Normal

2020 ◽  
Vol 21 (20) ◽  
pp. 7473
Author(s):  
Alip Ghosh ◽  
Sara Romani ◽  
Shyam Kottilil ◽  
Bhawna Poonia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Virologic Response ◽  
Viral Clearance ◽  
Liver Pathology ◽  
Direct Acting Antiviral ◽  
Chronic Hcv ◽  
Direct Acting ◽  
Immune Defects ◽  
The Impact

Chronic HCV (CHC) infection is the only chronic viral infection for which curative treatments have been discovered. These direct acting antiviral (DAA) agents target specific steps in the viral replication cycle with remarkable efficacy and result in sustained virologic response (SVR) or cure in high (>95%) proportions of patients. These treatments became available 6–7 years ago and it is estimated that their real impact on HCV related morbidity, including outcomes such as cirrhosis and hepatocellular carcinoma (HCC), will not be known for the next decade or so. The immune system of a chronically infected patient is severely dysregulated and questions remain regarding the immune system’s capacity in limiting liver pathology in a cured individual. Another important consequence of impaired immunity in patients cleared of HCV with DAA will be the inability to generate protective immunity against possible re-infection, necessitating retreatments or developing a prophylactic vaccine. Thus, the impact of viral clearance on restoring immune homeostasis is being investigated by many groups. Among the important questions that need to be answered are how much the immune system normalizes with cure, how long after viral clearance this recalibration occurs, what are the consequences of persisting immune defects for protection from re-infection in vulnerable populations, and does viral clearance reduce liver pathology and the risk of developing hepatocellular carcinoma in individuals cured with these agents. Here, we review the recent literature that describes the defects present in various lymphocyte populations in a CHC patient and their status after viral clearance using DAA treatments.

Learning the Roles of the Hepatic Adaptive Immune System in Hepatocellular Carcinoma—Nature's Guide for Successful Cancer Immunotherapy

2017 ◽  
Vol 37 (03) ◽  
pp. 210-218 ◽  
Author(s):  
Mathias Heikenwälder ◽  
Eli Pikarsky
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Immune Cells ◽  
Protective Immunity ◽  
Adaptive Immune System ◽  
Hepatic Parenchyma ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Pathophysiological Role

AbstractThe different roles of the adaptive immune system in cancer are beginning to unfold. The dramatic responses to immune check point drugs in some tumors generated an accelerated need for understanding the complex set of interactions between tumor and immune cells. In view of the major pathophysiological role of immune cells in hepatocellular carcinoma, it is not surprising that malignant hepatocytes interact extensively with adaptive immune cells, resulting in both protumor immunopathology and antitumor protective immunity. Identifying potential responders to drugs that target the adaptive immune system, monitoring their immune response to the tumor, and devising the best treatment combinations depends on understanding the complex set of interactions taking place within the tumor and in the adjacent hepatic parenchyma.

358 Trial in progress: A pilot study of combined immune checkpoint inhibition in combination with ablative therapies in subjects with hepatocellular carcinoma (HCC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A383-A383
Author(s):  
Hailey Carroll ◽  
Umair Aleem ◽  
Pooja Varghese ◽  
Marie Galligan ◽  
Michèle Bourke ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Response ◽  
Immune System ◽  
Immune Checkpoint ◽  
Innate Immune System ◽  
Innate Immune ◽  
University Hospital ◽  
Advanced Hepatocellular Carcinoma ◽  
Ablative Therapies

BackgroundLocoregional therapies for hepatocellular carcinoma, such as transcatheter arterial chemoembolization (TACE) or ablation, can induce a peripheral anti-tumor immune response. This may be amplified by immune checkpoint inhibitors (ICI). Early and higher anti-CTLA4 dosing could potentially lead to better priming and a stronger immune response. Recent data has suggested that early (Day 1 only), increased doses of anti-CTLA4 therapy, was associated with encouraging clinical activity and a tolerable safety profile. This study will evaluate dual immune checkpoint, CTLA4 (tremelimumab, day 1-only dosing) and PD-L1 (durvalumab) blockade in combination with TACE in patients with advanced HCC. Intensive peripheral immune-monitoring and longitudinal on-treatment tumor biopsies will focus on the role of the innate immune system, particularly Natural Killer cells, in anti-tumor responses.MethodsPatients with HCC (Childs Pugh A/B7; Barcelona Clinic Liver Cancer Stage B/C; ECOG 0/1; sorafenib-naïve or experienced) are being enrolled in a pilot study (Study Number UCDCRC/19/01) of tremelimumab at 2 dose levels (DL1 and DL2) in combination with durvalumab and TACE until disease progression (per irRECIST). DL1: tremelimumab (75 mg q28 days for 4 doses) and durvalumab (1500 mg q28 days). DL2: tremelimumab (300 mg in a single dose on day 1) and durvalumab (1500 mg q28 days). Subtotal TACE will be performed during study week 6 with the dose-limiting toxicity (DLT) evaluation period encompassing the first 8 weeks of the study. Primary endpoint is 6-month progression-free survival with secondary efficacy endpoints being safety, tolerability and overall survival. Exploratory objectives will evaluate changes in immune parameters in the tumor and peripheral blood of patients undergoing anti-CTLA4 therapy pre- and post-RFA or TACE. A major focus will be on the role of the innate immune system, particularly Natural Killer cells, in anti-tumor responses. Patients will be enrolled and treated at St Vincent’s University Hospital in Dublin, Ireland. This study is currently open and actively recruiting.ResultsN/AConclusionsN/ATrial RegistrationEudraCT Number 2019-002767-98Ethics ApprovalSt Vincent’s University Hospital Research Ethics Committee Study Number UCDCRC/19/01.ReferencesDuffy AG, Ulahannan SV, Makorova-Rusher O, Rahma O, Wedemeyer H, Pratt D, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol 2017;66(3):545–51.Lencioni R, Petruzzi P, Crocetti L. Chemoembolization of hepatocellular carcinoma. Semin Intervent Radiol 2013;30(1):3–11.Slovak R, Ludwig JM, Gettinger SN, Herbst RS, Kim HS. Immuno-thermal ablations – boosting the anticancer immune response.Mehta A, Oklu R, Sheth RA. Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional Approaches Effect a Systemic Response?Gastroenterol Res Pract2016; 2016:9251375.Ng J, Dai T. Radiation therapy and the abscopal effect: a concept comes of age. Ann Transl Med 2016;4(6):118.O’Brien MA, Power DG, Clover AJ, Bird B, Soden DM, Forde PF. Local tumour ablative therapies: opportunities for maximising immune engagement and activation. Biochim Biophys Acta2014; 1846(2):510–23.Kelley RK, Sangro B, Harris WP, Ikeda M, Okusaka T, Kang Y-K, et al. Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC). Journal of Clinical Oncology 2020;38(15_suppl):4508-.Mariniello A, Novello S, Scagliotti GV, Ramalingam SS. Double immune checkpoint blockade in advanced NSCLC. Crit Rev Oncol Hematol 2020;152:102980.

scholarly journals Spontaneous regression of hepatocellular carcinoma after improving diabetes mellitus: possibly responsible for immune system

Kanzo ◽  
2012 ◽  
Vol 53 (3) ◽  
pp. 164-174 ◽  
Author(s):  
Satoshi Yamamoto ◽  
Taigo Tokuhara ◽  
Masahiro Nishikawa ◽  
Satoshi Nishizawa ◽  
Takayosi Nishioka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Spontaneous Regression
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