Novel Molecular Targets for Immune Surveillance of Hepatocellular Carcinoma
Abstract
Simple Summary
Abstract
1. Introduction
2. The Immuno System in HCC
2.1. Antigen Recognition
2.2. Tumour Microenvironment
2.2.1. Adoptive Cell Therapy
2.2.2. Lymphoid Inhibiting Cells
T Regulatory Lymphocytes
2.2.3. Myeloid Inhibiting Cells
Tumour-Associated Macrophages (TAMs)
Myeloid-Derived Suppressor Cells (MDSCs)
Dendritic Cells
2.2.4. Non-Parenchymal Hepatic Cells
3. Immune Classification
3.1. The Inflamed Class: Immune-Active, Immune-Exhausted and Immune-like
3.2. The Non-Inflamed Class: Immune-Intermediate and Immune-Excluded
4. Role of SerpinB3 in the Immunosurveillance of HCC
Response to Hypoxic Conditions and HIF Induction
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Target Cell | Mechanism of Surveillance | Suggested Therapy | References | |
---|---|---|---|---|
Adoptive Cell Therapy | CAR-T | [45] | ||
TCR Engineered T cells | [41] | |||
Lymphoid cells | Tregs | Secretion of TGF-beta and IL-10. Inhibition of M1 activity. | Immune Checkpoint Inhibitors | [46] |
Myeloid cells | TAMs | Inhibition of CD8+. Stimulation of Tregs. Production of proangiogenic and pro-proliferation cytokines | Eliminating production | [47] |
Remodelling M2 polarization | ||||
Blocking communication with cancer | ||||
MDSCs | L-Arginine and nitric oxide synthase-2 pathway-dependent inhibition of cytotoxic response | PDE5 inhibitors | [48] | |
DCs | Antigen-presenting function. Boosting cytotoxic activity | Vaccine strategies | [49] | |
Non-parenchymal cells | KCs | Macrophages chemotaxis and polarization. Up-regulation of PD-1/PD-L1. | Blocking CCL2/CCR2 axis | [50] |
Platelets inhibition | [51] | |||
HSCs | Promotion of fibrosis and oncogenesis | Targeting molecular pathways of activation (e.g., TGF-beta) | [52] |
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Guerra, P.; Martini, A.; Pontisso, P.; Angeli, P. Novel Molecular Targets for Immune Surveillance of Hepatocellular Carcinoma. Cancers 2023, 15, 3629. https://doi.org/10.3390/cancers15143629
Guerra P, Martini A, Pontisso P, Angeli P. Novel Molecular Targets for Immune Surveillance of Hepatocellular Carcinoma. Cancers. 2023; 15(14):3629. https://doi.org/10.3390/cancers15143629
Chicago/Turabian StyleGuerra, Pietro, Andrea Martini, Patrizia Pontisso, and Paolo Angeli. 2023. "Novel Molecular Targets for Immune Surveillance of Hepatocellular Carcinoma" Cancers 15, no. 14: 3629. https://doi.org/10.3390/cancers15143629
APA StyleGuerra, P., Martini, A., Pontisso, P., & Angeli, P. (2023). Novel Molecular Targets for Immune Surveillance of Hepatocellular Carcinoma. Cancers, 15(14), 3629. https://doi.org/10.3390/cancers15143629