Abstract
The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present. However, the tolerogenic nature of the liver means that the immune response to infection, chronic inflammation and tumour cells within the hepatic environment is usually ineffective. Here we review the roles that immune cells and cytokines have in the development of the most common primary liver cancer, hepatocellular carcinoma (HCC). We then examine how the immune system may be subverted throughout the stages of HCC development, particularly with respect to immune inhibitory molecules, also known as immune checkpoints, such as programmed cell death protein-1, programmed cell death 1 ligand 1 and cytotoxic T lymphocyte antigen 4, which have become therapeutic targets. Finally, we assess preclinical and clinical studies where immune checkpoint inhibitors have been used to modify disease during the carcinogenic process. In conclusion, inhibitory molecule-based immunotherapy for HCC is in its infancy and further detailed research in relevant in vivo models is required before its full potential can be realised.
| Original language | English |
|---|---|
| Article number | 161 |
| Number of pages | 11 |
| Journal | Clinical & Translational Immunology |
| Volume | 6 |
| DOIs | |
| Publication status | Published - 10 Nov 2017 |
Cite this
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Immune checkpoint inhibition : prospects for prevention and therapy of hepatocellular carcinoma. / Elsegood, Caryn L.; Tirnitz-Parker, Janina E. E.; Olynyk, John K.; Yeoh, George C. T.
In: Clinical & Translational Immunology, Vol. 6, 161, 10.11.2017.Research output: Contribution to journal › Review article
TY - JOUR
T1 - Immune checkpoint inhibition
T2 - prospects for prevention and therapy of hepatocellular carcinoma
AU - Elsegood, Caryn L.
AU - Tirnitz-Parker, Janina E. E.
AU - Olynyk, John K.
AU - Yeoh, George C. T.
PY - 2017/11/10
Y1 - 2017/11/10
N2 - The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present. However, the tolerogenic nature of the liver means that the immune response to infection, chronic inflammation and tumour cells within the hepatic environment is usually ineffective. Here we review the roles that immune cells and cytokines have in the development of the most common primary liver cancer, hepatocellular carcinoma (HCC). We then examine how the immune system may be subverted throughout the stages of HCC development, particularly with respect to immune inhibitory molecules, also known as immune checkpoints, such as programmed cell death protein-1, programmed cell death 1 ligand 1 and cytotoxic T lymphocyte antigen 4, which have become therapeutic targets. Finally, we assess preclinical and clinical studies where immune checkpoint inhibitors have been used to modify disease during the carcinogenic process. In conclusion, inhibitory molecule-based immunotherapy for HCC is in its infancy and further detailed research in relevant in vivo models is required before its full potential can be realised.
AB - The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present. However, the tolerogenic nature of the liver means that the immune response to infection, chronic inflammation and tumour cells within the hepatic environment is usually ineffective. Here we review the roles that immune cells and cytokines have in the development of the most common primary liver cancer, hepatocellular carcinoma (HCC). We then examine how the immune system may be subverted throughout the stages of HCC development, particularly with respect to immune inhibitory molecules, also known as immune checkpoints, such as programmed cell death protein-1, programmed cell death 1 ligand 1 and cytotoxic T lymphocyte antigen 4, which have become therapeutic targets. Finally, we assess preclinical and clinical studies where immune checkpoint inhibitors have been used to modify disease during the carcinogenic process. In conclusion, inhibitory molecule-based immunotherapy for HCC is in its infancy and further detailed research in relevant in vivo models is required before its full potential can be realised.
KW - CD8(+) T-CELL
KW - CHRONIC VIRAL-INFECTION
KW - SINUSOIDAL ENDOTHELIAL-CELLS
KW - CHRONIC HEPATITIS-B
KW - C VIRUS-INFECTION
KW - DENDRITIC CELLS
KW - TH17 CELLS
KW - DISEASE PROGRESSION
KW - BLOCKADE SYNERGIZES
KW - ADAPTIVE IMMUNITY
U2 - 10.1038/cti.2017.47
DO - 10.1038/cti.2017.47
M3 - Review article
VL - 6
JO - Clinical & Translational Immunology
JF - Clinical & Translational Immunology
SN - 2050-0068
M1 - 161
ER -