scholarly journals Immunotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuoyan Liu ◽  
Xuan Liu ◽  
Jiaxin Liang ◽  
Yixin Liu ◽  
Xiaorui Hou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Rapid Development ◽  
Adoptive Cell Therapy ◽  
Research Field ◽  
Research Progress ◽  
Current Status ◽  
Challenges And Opportunities ◽  
Therapeutic Cancer Vaccines

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with poor prognosis. Surgery, chemotherapy, and radiofrequency ablation are three conventional therapeutic options that will help only a limited percentage of HCC patients. Cancer immunotherapy has achieved dramatic advances in recent years and provides new opportunities to treat HCC. However, HCC has various etiologies and can evade the immune system through multiple mechanisms. With the rapid development of genetic engineering and synthetic biology, a variety of novel immunotherapies have been employed to treat advanced HCC, including immune checkpoint inhibitors, adoptive cell therapy, engineered cytokines, and therapeutic cancer vaccines. In this review, we summarize the current landscape and research progress of different immunotherapy strategies in the treatment of HCC. The challenges and opportunities of this research field are also discussed.

scholarly journals Immunotherapy for Hepatocellular Carcinoma: Current Advances and Future Expectations

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yingjun Xie ◽  
Yien Xiang ◽  
Jiyao Sheng ◽  
Dan Zhang ◽  
Xiaoxiao Yao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Checkpoint Inhibitors ◽  
Ex Vivo ◽  
Primary Liver Cancer ◽  
Adoptive Cell Therapy ◽  
Oncolytic Viruses ◽  
Future Expectations ◽  
Digestive Cancers

Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis. Immune tolerance and suppression in tumor microenvironments are the theoretical basis of immunotherapy. Adoptive cell therapy functions by stimulating and cultivating autologous lymphocytes ex vivo and then reinfusing them into the patient to kill cancer cells. Cancer vaccination is performed using antigenic substances to activate tumor-specific immune responses. Immune checkpoint inhibitors can reactivate tumor-specific T cells and develop an antitumor effect by suppressing checkpoint-mediated signaling. Oncolytic viruses may selectively replicate in tumor cells and cause lysis without harming normal tissues. Here, we briefly introduce the mechanism of immunosuppression in hepatocellular carcinoma and summarize the rationale of the four major immunotherapeutic approaches with their current advances.

scholarly journals Application of Immunotherapy in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Lele Miao ◽  
Zhengchao Zhang ◽  
Zhijian Ren ◽  
Yumin Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Therapy ◽  
Immune Responses ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Adoptive Cell Therapy ◽  
Research Progress ◽  
Tumor Vaccines ◽  
Immunosuppressive Microenvironment

Hepatocellular carcinoma is one of the most common malignancies globally. It not only has a hidden onset but also progresses rapidly. Most HCC patients are already in the advanced stage of cancer when they are diagnosed, and have even lost the opportunity for surgical treatment. As an inflammation-related tumor, the immunosuppressive microenvironment of HCC can promote immune tolerance through a variety of mechanisms. Immunotherapy can activate tumor-specific immune responses, which brings a new hope for the treatment of HCC. At the present time, main immunotherapy strategies of HCC include immune checkpoint inhibitors, tumor vaccines, adoptive cell therapy, and so on. This article reviews the application and research progress of immune checkpoint inhibitors, tumor vaccines, and adoptive cell therapy in the treatment of HCC.

scholarly journals Integration of Digital Economy and Circular Economy: Current Status and Future Directions

2021 ◽  
Vol 13 (13) ◽  
pp. 7217
Author(s):  
Zhen Liu ◽  
Jing Liu ◽  
Mohamed Osmani
Keyword(s):  
Circular Economy ◽  
Digital Technology ◽  
Global Economy ◽  
Digital Economy ◽  
Research Field ◽  
Research Progress ◽  
Current Status ◽  
Future Research ◽  
Disruptive Effect ◽  
The European Union

Circular economy (CE) is a concept actively advocated by the European Union (EU), China, Japan, and the United Kingdom. At present, CE is considered to grant the most traction for companies to achieve sustainable development. However, CE is still rarely adopted by enterprises. As the backbone of the fourth industrial revolution, the digital economy (DE) is considered to have a disruptive effect. Studies have shown that digital technology has great potential in promoting the development of CE. Especially during the COVID-19 epidemic that has severely negatively affected the global economy, environment, and society, CE and DE are receiving high attention from policy makers, practitioners, and scholars around the world. However, the integration of CE and digital technology is a small and rapidly developing research field that is still in its infancy. Although there is a large amount of research in the fields of CE and DE, respectively, there are few studies that look into integrating these two fields. Therefore, the purpose of this paper is to explore the research progress and trends of the integration of CE and DE, and provide an overview for future research. This paper adopts a bibliometric research method, employs the Web of Science database as its literature source, and uses VOSviewer visual software to carry out keyword co-occurrence analysis, which focuses on publication trends, journal sources, keyword visualization, multidisciplinary areas, life cycle stages, and application fields.

scholarly journals Immunotherapy in Hepatocellular Carcinoma: Is There a Light at the End of the Tunnel?

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1078 ◽  
Author(s):  
Amit Mahipal ◽  
Sri Harsha Tella ◽  
Anuhya Kommalapati ◽  
Alexander Lim ◽  
Richard Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Progression Free Survival ◽  
The United States ◽  
Hepatic Reserve ◽  
Dismal Prognosis ◽  
United States Food

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with dismal prognosis when diagnosed at advanced stages. Surgical resection of the primary tumor or orthotropic liver transplantation serves as a potential curative option. However, this approach is highly dependent on the hepatic reserve and baseline functional status of the patient. Liver directed therapies such as portal vein embolization (PVE), trans-arterial chemoembolization (TACE), and systemic chemotherapy are employed in non-surgical candidates. Sorafenib was the only approved systemic therapeutic agent for almost a decade until the recent approval of lenvatinib by the United States Food and Drug Administration (FDA) as an alternate first-line agent. Regorafenib, nivolumab, pembrolizumab and cabozantinib are approved by the FDA as second-line agents in patients who failed or could not tolerate sorafenib. Ramucirumab was recently FDA approved for the subset of patients that have high alfa-fetoprotein levels (>400 ng/mL). A better understanding of tumorigenesis and encouraging clinical trial results that evaluated immune-checkpoint inhibitors opened doors for immunotherapy in HCC. Immune checkpoint inhibitors have demonstrated a prolonged median overall and progression-free survival in a subset of patients with HCC. On-going translational and clinical research will hopefully provide us with a better understanding of tumor markers, genetic aberrations and other factors that determine the immunotherapy response in HCC. In this review, we sought to summarize the potential role and future directions of immunotherapy in the management of HCC.

scholarly journals Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Progresses and Challenges

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao-Tian Liu ◽  
Meng-Jie Jiang ◽  
Zhu-Jian Deng ◽  
Le Li ◽  
Jian-Li Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Research Progress ◽  
T Cell Signaling ◽  
Existing Problems ◽  
Programmed Death ◽  
New Treatment

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world and its incidence is increasing in many countries. In recent years, with the deepening understanding of the immune and pathological mechanisms of HCC, immunotherapy based on the regulation of tumor immune microenvironment has become a new treatment choice for patients with HCC. Immune checkpoint inhibitors (ICIs) targeting programmed death protein-1, programmed death protein-ligand-1, or cytotoxic T-lymphocyte-associated antigen 4 are the most widely used. Instead of general immune-enhancing therapies, ICIs can reactivate anti-tumor immune responses by disrupting co-inhibitory T cell signaling. In this review, the research progress and existing problems of ICIs in the treatment of HCC in recent years are reviewed.

scholarly journals Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Status and Novel Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3025
Author(s):  
Piera Federico ◽  
Angelica Petrillo ◽  
Pasqualina Giordano ◽  
Davide Bosso ◽  
Antonietta Fabbrocini ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Critical Evaluation ◽  
Phase Iii ◽  
Current Status ◽  
Small Subset ◽  
Second Line

Immune checkpoint inhibitors (ICIs) represent a promising treatment for many kinds of cancers, including hepatocellular carcinoma (HCC). The rationale for using ICIs in HCC is based on the immunogenic background of hepatitis and cirrhosis and on the observation of high programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes in this cancer. Promising data from phase I/II studies in advanced HCC, showing durable objective response rates (~20% in first- and second-line settings) and good safety profile, have led to phase III studies with ICIs as single agents or in combination therapy, both in first and second line setting. While the activity of immunotherapy agents as single agents seems to be limited to an “ill-defined” small subset of patients, the combination of the anti PD-L1 atezolizumab and anti-vascular endothelial growth factor bevacizumab revealed a benefit in the outcomes when compared to sorafenib in the first line. In addition, the activity and efficacy of the combinations between anti-PD-1/anti-PD-L1 antibody and other ICIs, tyrosine kinase inhibitors, or surgical and locoregional therapies, has also been investigated in clinical trials. In this review, we provide an overview of the role of ICIs in the management of HCC with a critical evaluation of the current status and future directions.

scholarly journals Combining Chemistry and Engineering for Hepatocellular Carcinoma: Nano-Scale and Smaller Therapies

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1243
Author(s):  
Danielle L. Stolley ◽  
Anna Colleen Crouch ◽  
Aliçan Özkan ◽  
Erin H. Seeley ◽  
Elizabeth M. Whitley ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Residual Disease ◽  
Primary Liver Cancer ◽  
Intermediate Stage ◽  
Model Systems ◽  
Current Status ◽  
Label Free ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Stage Disease ◽  
New Applications

Primary liver cancer, or hepatocellular carcinoma (HCC), is a major worldwide cause of death from carcinoma. Most patients are not candidates for surgery and medical therapies, including new immunotherapies, have not shown major improvements since the modest benefit seen with the introduction of sorafenib over a decade ago. Locoregional therapies for intermediate stage disease are not curative but provide some benefit. However, upon close scrutiny, there is still residual disease in most cases. We review the current status for treatment of intermediate stage disease, summarize the literature on correlative histopathology, and discuss emerging methods at micro-, nano-, and pico-scales to improve therapy. These include transarterial hyperthermia methods and thermoembolization, along with microfluidics model systems and new applications of mass spectrometry imaging for label-free analysis of pharmacokinetics and pharmacodynamics.

scholarly journals Locoregional Combined With Systemic Therapies for Advanced Hepatocellular Carcinoma: An Inevitable Trend of Rapid Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Xin Li ◽  
Yaxi Wang ◽  
Xin Ye ◽  
Ping Liang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rapid Development ◽  
Locoregional Therapy ◽  
Current Status ◽  
Advanced Hepatocellular Carcinoma ◽  
Antitumor Effects ◽  
Primary Tumors ◽  
Advanced Hcc ◽  
Number Of Patients ◽  
Locoregional Therapies

Despite the application of antiviral drugs and improved surveillance tools, the number of patients diagnosed with hepatocellular carcinoma (HCC) at an advanced stage and with a dismal prognosis is still on the rise. Systemic treatment with multiple multitargeted tyrosine kinase inhibitors (TKIs), such as sorafenib, has been a widely utilized approach for a decade. In addition, the use of a combination of TKIs with other types of compounds, including immune checkpoint inhibitors (ICIs) and antiangiogenic inhibitors, has shown efficacy in treating advanced HCC. However, the presence of intolerable adverse events, low disease response and control rates, and relative short overall survival of such combinatory therapies makes novel or optimized therapies for advance HCC urgently needed. Locoregional therapy (transarterial chemoembolization, and thermal ablation) can destroy primary tumors and decrease tumor burden and is widely used for HCC management. This type of treatment modality can result in local hypoxia and increased vascular permeability, inducing immunogenic effects by releasing tumor antigens from dying cancer cells and producing damage-associated molecular patterns that facilitate antiangiogenic therapy and antitumor immunity. The combination of systemic and locoregional therapies may further produce synergistic effects without overlapping toxicity that can improve prognoses for advanced HCC. In preliminary studies, several combinations of therapeutic modes exhibited promising levels of safety, feasibility, and antitumor effects in a clinical setting and have, thus, garnered much attention. This review aims to provide a comprehensive, up-to-date overview of the underlying mechanisms of combined systemic and locoregional therapies in the treatment of advanced HCC, commenting on both their current status and future direction.

scholarly journals The role of the innate immune system in the development and treatment of hepatocellular carcinoma

2020 ◽  
Vol 7 (1) ◽  
pp. HEP17 ◽  
Author(s):  
Christoph Roderburg ◽  
Alexander Wree ◽  
Münevver Demir ◽  
Moritz Schmelzle ◽  
Frank Tacke
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Tyrosine Kinases ◽  
Innate Immune System ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Innate Immune ◽  
Dismal Prognosis ◽  
Liver Disease Progression

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Most patients present with advanced or metastatic HCC at diagnosis and face a dismal prognosis. Tyrosine kinases are the gold standard treatment for this disease but yield limited survival benefits. Immune checkpoint inhibitors that augment adaptive immunity have been tested in HCC. Complex interactions between tumor cells, lymphocytes and the tumor environment determine the efficacy of such immunotherapies. Innate immune mechanisms – known drivers of liver disease progression in pre-HCC conditions such as fibrosis or cirrhosis – may either support or counteract tumor-related immune activation. In this review, we will highlight current concepts of the role of the innate immune system in hepatocarcinogenesis and discuss their relevance for translation into clinics.

Research Progresses of Targeted Therapy and Immunotherapy for Hepatocellular Carcinoma

2020 ◽  
Vol 27 ◽  
Author(s):  
Tao Wang ◽  
Qiting Zhang ◽  
Ning Wang ◽  
Ziqi Liu ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapy ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Modern Medicine ◽  
Vital Role ◽  
Research Progress ◽  
Molecular Targeting Drug ◽  
Further Development ◽  
Made In

: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with nearly one million new cases and deaths every year. Owing to the complex pathogenesis, hidden early symptoms, rapidly developing processes and poor prognosis, the morbidity and mortality of HCC are increasing yearly. With the progress being made in modern medicine, the treatment of HCC is no longer limited to traditional methods. Targeted therapy and immunotherapy have emerged to treat advanced and metastatic HCC in recent years. Since Sorafenib is the first molecular targeting drug against angiogenesis, targeted drugs for HCC are continually emerging. Moreover, immunotherapy plays a vital role in clinical trials. In particular, the application of immune checkpoint inhibitors, which have received increasing attention in the field of cancer treatment, is a possible research path. Interestingly, these two therapies generally complement each other at some stages of HCC, bringing new hope for patients with advanced HCC. In this paper, we discuss the research progress of targeted therapy and immunotherapy for HCC in recent years, which will provide a reference for the further development of drugs for HCC.

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