The Interplay between the Immune and the Endocannabinoid Systems in Cancer
Abstract
1. Introduction
2. The Endocannabinoid System (ECS)
2.1. Receptors
Other Endocannabinoidome Receptors
2.2. Enzymes
3. Cannabinoids and Tumorigenesis
4. The Endocannabinoid System as Gate-Keeper of the Immune System
5. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
2-AG | 2-arachidonoylglycerol |
AEA or anandamide | N-arachidonoylethanolamide |
ANGPT | angiopoietin |
APC | antigen-presenting cell |
B cell | B lymphocyte |
BAD | BCL2 associated agonist of cell death |
BMMC | bone-marrow-derived mast cell |
cAMP | cyclic adenosine monophosphate |
CB | cannabinoid |
CBD | cannabidiol |
Cdk | cyclin-dependent kinase |
CLL | chronic lymphocytic leukemia |
CNS | central nervous system |
COX | cyclooxygenase |
CSC | cancer stem cells |
CXCR4 | C-X-C chemokine receptor type 4 |
DC | dendritic cell |
EC | endocannabinoid |
ECS | endocannabinoid system |
EGF | epidermal growth factor |
EMT | epithelial–mesenchymal transition |
ERK | extracellular receptor kinase |
FAAH | fatty acid amide hydrolase |
GCS | glioblastoma stem-like cells |
HGF | hepatocyte growth factor |
HLM | human lung macrophage |
IFN | interferon |
IL | interleukin |
LPS | lipopolysaccharide |
MAGL | monoacylglycerol lipase |
MAPK | mitogen-activated protein kinase |
MCL | mantle cell lymphoma |
MCs | mast cells |
MDM | monocyte-derived macrophage |
MMP | matrix metalloproteinase |
NK cell | natural killer cell |
OEA | oleoylethanolamide |
pDC | plasmacytoid dendritic cell |
PEA | palmitoylethanolamide |
PI3K | phosphoinositide 3-kinase |
PKB | pro-tumorigenic protein kinase B |
PIGF | placental growth factor |
PMN | neutrophil |
PPAR | peroxisome proliferator-activated receptors |
ROS | reactive oxygen species |
SCB | synthetic cannabinoid |
T cell | T lymphocyte |
Th cell | T helper cell |
TIMP | tissue inhibitors of metalloproteinases |
TLR | toll-like receptor |
TME | tumor microenvironment |
TNF | tumor necrosis factor |
TRB3 | Tribbles homolog 3 |
TRP | transient receptor potential channels |
VEGF | vascular endothelial growth factor |
Δ9-THC | Δ9-tetrahydrocannabinol. |
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Immune Cells | Effects of Cannabinoids and CB Receptor Ligands | Ligands | References |
---|---|---|---|
T Cells (human, mouse) | Inhibition of T cell proliferation | AEA | [180] |
Inhibition of cytolytic activity | Δ9-THC | [182] | |
Modulation of TH1/TH2 subsets | Δ9-THC | [181] | |
Inhibition of IL-2 expression | AEA, 2-AG | [183] | |
Inhibition of proliferation and cytokine release | JWH-015, AEA | [179,288] | |
Up-regulation of CB receptors | Δ9-THC, JWH-015 | [177] | |
Inhibition of T cell migration | AEA, JWH-133 | [289] | |
Treg Cells | Up-regulation of Tregs | Δ9-THC | [186] |
Macrophages (human, mouse, rat) | LPS and PAF induce the synthesis of 2-AG | [197,200] | |
Inhibition of migration | CP55, 940 | [196] | |
Inhibition of chemotaxis | O-2137 | [202] | |
Modulation of phagocytosis | 2-AG | [203] | |
Inhibition of macrophage cytotoxicity | AEA | [204] | |
Inhibition of IL-6 release | Δ9-THC, 2-AG | [198] | |
Inhibition of TNF-α | 2-AG | [290] | |
Promotion of ROS production | ACEA | [291] | |
Inhibition of angiogenic factor release | ACEA, JWH-133 | [29] | |
Inhibition of lymphangiogenic factor release | ACEA, JWH-133 | [29] | |
Neutrophils (human) | Inhibition of ROS production | 2-AG | [215] |
Inhibition of chemotaxis | AEA | [51] | |
Inhibition of motility | 2-AG, JWH-015 | [212] | |
Inhibition of angiogenic factor release | ACEA, JWH-133 | [46] | |
Promotion of myeloperoxidase release | 2-AG | [292] | |
Promotion of LTB4 synthesis | 2-AG | [292] | |
Mast Cells (human, guinea pig, mouse) | Inhibition of histamine release | 2-AG, AEA | [225,230] |
Inhibition of activation of skin mast cells | AEA, ACEA | [226] | |
Inhibition of TNF-α secretion | 2-AG | [229] | |
Inhibition of cytokine release | AEA | [230] | |
Modulation of angiogenesis | ACEA, JWH-015 | [227] | |
Monocytes (human) | Promotion of migration | 2-AG | [235] |
Inhibition of chemotaxis | JWH-015 | [236] | |
Inhibition of ICAM-1 expression | JWH-015 | [236] | |
Inhibition of cytokine release | AEA | [238] | |
Modulation of ROS production | AEA, ACEA, WH-015 | [291] | |
Natural Killer Cells (human, mouse) | Inhibition of cytolytic activity | Δ9-THC | [241,242,243,244] |
Promotion of migration | 2-AG | [245] | |
Modulation of lung NK cells | AM630 | [246] | |
Dendritic Cells (human, mouse) | Induction of apoptosis | Δ9-THC | [250] |
Promotion of chemotaxis | 2-AG | [252] | |
Inhibition of cytokine release | AEA | [253] | |
B cells (human) | B-cell differentiation | 2-AG | [265] |
Accumulation of ceramide | Win55 | [269] | |
Promotion of migration | 2-AG | [293,294,295] | |
Eosinophils (human, mouse) | Promotion of chemotaxis | 2-AG, JWH-133 | [275,276,277] |
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Braile, M.; Marcella, S.; Marone, G.; Galdiero, M.R.; Varricchi, G.; Loffredo, S. The Interplay between the Immune and the Endocannabinoid Systems in Cancer. Cells 2021, 10, 1282. https://doi.org/10.3390/cells10061282
Braile M, Marcella S, Marone G, Galdiero MR, Varricchi G, Loffredo S. The Interplay between the Immune and the Endocannabinoid Systems in Cancer. Cells. 2021; 10(6):1282. https://doi.org/10.3390/cells10061282
Chicago/Turabian StyleBraile, Mariantonia, Simone Marcella, Gianni Marone, Maria Rosaria Galdiero, Gilda Varricchi, and Stefania Loffredo. 2021. "The Interplay between the Immune and the Endocannabinoid Systems in Cancer" Cells 10, no. 6: 1282. https://doi.org/10.3390/cells10061282
APA StyleBraile, M., Marcella, S., Marone, G., Galdiero, M. R., Varricchi, G., & Loffredo, S. (2021). The Interplay between the Immune and the Endocannabinoid Systems in Cancer. Cells, 10(6), 1282. https://doi.org/10.3390/cells10061282