Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer
Abstract
:1. Introduction
2. Crosstalk of DCs and T Cells
2.1. DCs in the Liver
2.2. T Cells in the Liver
2.3. DC and T Cell Interaction in the Liver
3. Fibrosis and Cirrhosis
3.1. DCs in Liver Fibrosis
3.2. T Cells in Liver Fibrosis
4. Carcinogenesis and HCC
4.1. DCs in HCC
4.2. Tumor Microenvironment
4.3. Tregs
4.4. Lymphocyte Function in HCC
5. Immunological Therapeutic Approaches
5.1. Immune Checkpoint Inhibition
5.2. DC-Based Vaccines
5.3. Oncolytic Immunotherapies
5.4. Combination of Checkpoint Inhibitors
6. Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ALD | Alcohol-related liver disease |
APC | Antigen-presenting cell |
BDL | Bile duct ligation |
CAF | Cancer-associated fibroblasts |
CCL | Chemokine (C-C motif) ligand |
CCl4 | Carbon tetrachloride |
CCR | C-C chemokine receptor type |
cDC | Conventional dendritic cell |
CTLA | Cytotoxic T-lymphocyte antigen |
DC | Dendritic cell |
DFS | Disease-free survival |
DTR | Diphtheria toxin receptor |
ECM | Extracellular matrix |
EGF | Epidermal growth factor |
FDA | Food and Drug Administration |
Flt3L | Fms-like tyrosine kinase 3 ligand |
GM-CSF | Granulocyte-macrophage colony-stimulating factor |
GRO-α | Growth-related oncogene α |
HCC | Hepatocellular carcinoma |
HLA | Human leukocyte antigen |
HSC | Hepatic stellate cell |
ICAM | Intercellular adhesion molecule |
ICOS-L | Inducible co-stimulatory ligand |
IDO | Indoleamine 2,3-dioxygenase |
IL | Interleukin |
infDC | Inflammatory dendritic cell |
LAG3 | Lymphocyte-activation gene 3 |
LPS | Lipopolysaccharides |
LSEC | Liver sinusoidal cell |
MCD | Methionine/choline-deficient |
MDSC | Myeloid-derived suppressor cells |
MHC | Major histocompatibility complex |
MMP | Matrix metalloproteinase |
moDC | Monocyte-derived dendritic cell |
NASH | Nonalcoholic steatohepatitis |
NK | Natural killer |
OS | Overall survival |
PD-1 | Programmed cell death protein 1 |
PD-L1 | Programmed cell death 1 ligand 1 |
pDC | Plasmacytoid dendritic cell |
PDGF | Platelet-derived growth factor |
ROS | Reactive oxygen species |
sFlt-1 | Soluble vascular endothelial growth factor receptor 1 |
TA | Tumor-associated antigen |
TAP | Transporter associated with antigen processing |
TGF | Transforming growth factor |
TAM | Tumor-associated macrophage |
TIM1 | T cell immunoglobulin and mucin-domain containing-3 |
TIMP1 | Tissue inhibitor of metalloproteinases |
TLR | Toll-like receptor |
TME | Tumor microenvironment |
TNF | Tumor necrosis factor |
Tregs | Regulatory T cells |
VAP1 | Vascular adhesion protein 1 |
VCAM | Vascular cellular adhesion molecule |
VEGF | Vascular endothelial growth factor |
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Population | Marker | Properties/Function | ||
---|---|---|---|---|
Human | Mice | |||
cDC | Type 1 | CD141, CD8, BATF3, IRF8, Clec9a, XCR1, TLR3 | CD103, CD8, BATF3, IRF8, Clec9a, XCR1, TLR3 | CD8+ T cell activation and cross-presentation [30], TLR2, TLR4 |
Type 2 | CD1c, CD11b | CD11b, IRF4 | T helper cell priming with polarization toward Th2 or Th17 and promotion of humoral immunity [30]. Overall rare, but most frequent DC type in the human liver [25]. Secrete IL-10 upon TLR4 stimulation and induce T cell hyporesponsiveness [25]. Further subsets can be distinguished based on CD5, CD163 and CD14 expression, one of them is a circulating inflammatory (CD5-CD163+CD14+) subtype [28] | |
Pdc (precursors) | CD303, CD304, CD4, CD123high, TLR-7, TLR9 | CD11c+ B220+ Gr-1+, TLR7, CD45Rbhigh [26,31] | Antiviral innate immunity: antiviral response with abundant type 1 IFN production, stimulation of B cells, NK cells and T cells, differentiate into mature dendritic cells with intense T cell interaction [26] and capable of cross-presentation [32]. | |
moDC | DC-SIGN(+) | Monocytes adopt a dendritic function and morphology in the presence of lipopolysaccharides or Gram-negative bacteria [33]. Used in vitro to model the DC function. |
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Lurje, I.; Hammerich, L.; Tacke, F. Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer. Int. J. Mol. Sci. 2020, 21, 7378. https://doi.org/10.3390/ijms21197378
Lurje I, Hammerich L, Tacke F. Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer. International Journal of Molecular Sciences. 2020; 21(19):7378. https://doi.org/10.3390/ijms21197378
Chicago/Turabian StyleLurje, Isabella, Linda Hammerich, and Frank Tacke. 2020. "Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer" International Journal of Molecular Sciences 21, no. 19: 7378. https://doi.org/10.3390/ijms21197378