Ubiquitination in hepatocellular carcinoma immunity
Jianan Zhao1,2, Yuxuan Li1,2, Jie Zhu1
1Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, 315040, P. R. China.
Journal of Translational Medicine
|May 23, 2025
Summary
Ubiquitination regulates immune responses in hepatocellular carcinoma (HCC). Targeting ubiquitination pathways can enhance immunotherapy and overcome resistance in advanced HCC, offering new treatment strategies.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Hepatocellular carcinoma (HCC) is a major global health challenge, with advanced stages having poor prognosis.
- Immune system dysregulation is central to HCC pathogenesis and progression.
- Ubiquitination, a post-translational modification, critically regulates immune homeostasis in HCC.
Purpose of the Study:
- To elucidate the interplay between ubiquitination networks and HCC-related immune dysregulation.
- To analyze how ubiquitination drives hepatocarcinogenesis via chronic inflammation.
- To evaluate clinical advances combining ubiquitination-targeted therapies with immunotherapies.
Main Methods:
- Review of mechanistic insights into ubiquitination's role in innate and adaptive immunity in HCC.
- Systematic analysis of ubiquitination's impact on inflammatory pathways and hepatocarcinogenesis.
- Critical evaluation of clinical data on combined ubiquitination-targeted and immunotherapeutic regimens.
Main Results:
- Ubiquitination modulates immune cell activation, differentiation, and tolerance.
- Ubiquitination influences innate immune signaling (NF-κB, STING) and adaptive immunity (T cell receptor).
- Targeting ubiquitination enhances PD-1/PD-L1 blockade efficacy and mitigates resistance by modulating tumor microenvironment.
Conclusions:
- Strategic manipulation of ubiquitination pathways can potentiate immunotherapy efficacy in HCC.
- Ubiquitination-immune axis modulation offers a framework for novel diagnostic biomarkers and therapeutic combinations.
- This approach holds potential to transform HCC management and advance precision immunotherapy.
More Related Videos
Related Concept Videos
01:15Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:26Antigens Involved in Adaptive Immunity
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
01:27Cytotoxic T Cells-mediated Immune Response
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:27Tumor Immunotherapy
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:24Liver Regeneration
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...