Current Status and Future Direction of Immunotherapy in Hepatocellular Carcinoma: What Do the Data Suggest?

Immune Network
Hye Won LeeJun Yong Park

Abstract

Most patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage of disease. Until recently, systemic treatment options that showed survival benefits in HCC have been limited to tyrosine kinase inhibitors, antibodies targeting oncogenic signaling pathways or VEGF receptors. The HCC tumor microenvironment is characterized by a dysfunction of the immune system through multiple mechanisms, including accumulation of various immunosuppressive factors, recruitment of regulatory T cells and myeloid-derived suppressor cells, and induction of T cell exhaustion accompanied with the interaction between immune checkpoint ligands and receptors. Immune checkpoint inhibitors (ICIs) have been interfered this interaction and have altered therapeutic landscape of multiple cancer types including HCC. In this review, we discuss the use of anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies in the treatment of advanced HCC. However, ICIs as a single agent do not benefit a significant portion of patients. Therefore, various clinical trials are exploring possible synergistic effects of combinations of different ICIs (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies) or ICIs and target agents. Combinations of ICIs with locoregional therapi...Continue Reading

References

Jul 25, 2008·The New England Journal of Medicine·Josep M LlovetUNKNOWN SHARP Investigators Study Group
Jun 25, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Bastian HoechstFirouzeh Korangy
Jun 25, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Valerie DardalhonVijay K Kuchroo
Jul 28, 2010·Gut·Nidal MuhannaRifaat Safadi
Aug 4, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Melanie B ThomasAlan Venook
May 20, 2011·Clinical and Experimental Immunology·M YamamotoT Takehara
Mar 23, 2012·Nature Reviews. Immunology·Dmitry I GabrilovichVincenzo Bronte
Mar 24, 2012·Cancer Cell·Douglas Hanahan, Lisa M Coussens
Sep 21, 2013·Nature Immunology·Craig N Jenne, Paul Kubes
Oct 21, 2015·Nature Reviews. Gastroenterology & Hepatology·Jesús PrietoBruno Sangro
Jul 28, 2016·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Hae Il JungMoo-Jun Baek
Nov 7, 2016·Journal of Hepatology·Austin G DuffyTim F Greten
Nov 16, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mercedes IñarrairaeguiBruno Sangro
Dec 19, 2017·Clinical and Molecular Hepatology·Bo Hyun Kim, Joong-Won Park
Apr 7, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jorge A MarreroJulie K Heimbach
Apr 10, 2018·Journal of Hepatology·UNKNOWN European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, UNKNOWN European Association for the Study of the Liver
Jul 5, 2018·The New England Journal of Medicine·Ghassan K Abou-AlfaRobin K Kelley
Oct 24, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jianming XuQuanren Wang
Feb 13, 2019·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Jae Seung LeeJun Yong Park
Apr 2, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shao-Lai ZhouJian Zhou
Jun 7, 2019·World Journal of Gastroenterology : WJG·Changhoon ChoiHee Chul Park
Jun 14, 2019·Liver Cancer·Masatoshi Kudo
Jul 18, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Elisabetta Cariani, Gabriele Missale
Aug 20, 2019·Journal of Vascular and Interventional Radiology : JVIR·Chenyang ZhanRyan M Hickey
Sep 11, 2019·Journal of Experimental & Clinical Cancer Research : CR·Yaojie FuHong Shen
Dec 4, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Richard S FinnUNKNOWN KEYNOTE-240 investigators

❮ Previous
Next ❯

Citations

May 13, 2020·Journal for Immunotherapy of Cancer·Alberto PucciniMohamed E Salem
Jan 23, 2021·Expert Opinion on Drug Delivery·Andrew S MikhailBradford J Wood
Mar 6, 2021·Cellular and Molecular Gastroenterology and Hepatology·Jie ZanShuai Wang
May 29, 2021·Korean Journal of Radiology : Official Journal of the Korean Radiological Society·Luca RussoRiccardo Manfredi
Jun 3, 2021·International Journal of Molecular Sciences·Kyoko OuraTsutomu Masaki
May 18, 2021·Acta Pharmaceutica Sinica. B·Qingqing XiaoWei He
Jun 9, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kyungjoo ChoDo Young Kim
Jul 17, 2021·Cell Biology International·Ishfaq Hassan MirChinnasamy Thirunavukkarasu

❮ Previous
Next ❯

Clinical Trials Mentioned

NCT01658878
NCT02576509
NCT02423343
NCT02702414
NCT02702401
NCT03006926
NCT03412773
NCT02989922
NCT03092895
NCT03794440

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.