PDAC, the Influencer Cancer: Cross-Talk with Tumor Microenvironment and Connected Potential Therapy Strategies
Abstract
:Simple Summary
Abstract
1. Introduction
2. Review Strategies and Literature Included
3. PDAC TME
3.1. Acellular Component of PDAC TME
3.2. PSCs and CAFs
3.3. Immune Cells
3.3.1. Macrophages
3.3.2. Lymphocytes
3.3.3. Neutrophils
3.3.4. Mast Cells
3.4. Cross-Talk between PDAC and TME
3.5. The Role of TME from Precancerous Lesions to PDAC
4. Conventional Treatment in Resectable Pancreatic Cancers
5. New Therapeutical Strategies against PDCA
5.1. Pathway Inhibition
5.2. DNA Repair
5.3. Immunotherapy
Extracellular Tumor Microenvironment
5.4. CAR-T and CAR-M Cell Therapy
5.4.1. First Use of CAR T Cell Therapy
5.4.2. CAR-T Cell Therapy in Solid Tumors: Pancreatic Cancer
5.4.3. Side Effects of CAR-T Cell Therapy
5.4.4. CAR-M Cell Therapy as Another Chance towards Solid Malignancies
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ADM | Acinar-Ductal Metaplasia |
αKG | α-ketoglutarate |
AKT | Protein Kinase B |
apCAFs | Antigen-Presenting Cancer-Associated Macrophages |
APCs | Antigen-Presenting Cells |
ARID1A | AT-rich interactive domain-containing protein 1A |
α-SMA | α-Smooth Muscle Actin |
BM | Bone Marrow |
B-reg | Regulatory B Lymphocytes |
C1Q | complement component 1q |
CAFs | Cancer-Associated Fibroblasts |
CAR-T | chimeric antigen receptor T-cell therapy |
CAR-M | chimeric antigen receptor macrophages therapy |
CARTmeso cells | Mesothelin-directed CAR-T cells |
CCL2 | C-C Chemokine Ligand |
CD | Cluster of Differentiation |
CD133 | Prominin1 |
CDKN2A | cyclin-dependent kinase inhibitor 2A |
CEA | Carcinoembryonic Antigen |
CEACAM | CEA-related cell adhesion molecule |
CICs | Cancer Inducing Cells |
Col1a1 | Collagen, type I, alpha 1 |
Co-SMAD | co-mediator SMAD |
csCAFs | Complement-Secreting Cancer-Associated Macrophages |
CTLs | Cytotoxic T Lymphocytes |
CXCL | C-X-C motif Chemokine ligand |
DCs | Dendritic Cells |
ECM | Extracellular Matrix |
EMT | Epithelial-Mesenchymal Transition |
ERK | Extracellular signal-regulated kinase |
EVs | Extracellular Vesicles |
FAP | Fibroblast Activation Protein |
FGF | Fibroblasts Growth Factor |
FOXP3 | Forkhead box P3 |
FSP-1 | Fibroblast Surface Protein 1 |
GAGs | glycosaminoglycans |
GM-CSF | Granulocyte-Macrophage Colony Stimulating Factor |
GREM1 | Gremlin 1 |
HRAS | Harvey rat sarcoma viral |
HLA | Human Leukocyte Antigen |
HLA-DR | Human Leukocyte Antigen-DR isotype |
iCAFs | Inflammatory Cancer-Associated Fibroblasts |
IHH | Indian Hedgehog |
IL | Interleukin |
IPMN | intraductal papillary mucinous neoplasm |
KRAS | Kirsten Rat Sarcoma Virus |
M-CSF | Macrophage-Colony Stimulating Factor |
MAGUK | Membrane-Associated Guanylate Kinase |
MCL-1 | myeloid cell leukemia-1 |
MDSCs | Myeloid-Derived Suppressor Cells |
MHC | Major Histocompatibility Complex |
MIF | Macrophage Migration Inhibiting Factor |
MMPs | Matrix Metalloproteinases |
MMR | Mismatch Repair |
MPP6 | MAGUK P55 Subfamily Member |
MSCs | Mesenchymal Stem Cells |
MVBs | Multivesicular Bodies |
MYC | myelocytomatosis oncogene |
myCAFs | Myofibroblastic Cancer-Associated Macrophages |
NETs | Neutrophil Extracellular Traps |
NRAS | (Neuroblasoma rat sarcoma viral |
NK | Natural Killer |
NLRP3 | NLR family pyrin domain containing 3 |
Onf-FN | oncofetal Fibronectin |
PanIN | Pancreatic Intraepithelial Neoplasia |
PB | Peripheral Blood |
PC | Pancreatic Cancer |
PCCs | Pancreatic Cancer Cells |
PDAC | Pancreatic Ductal Adenocarcinoma |
PDGFR | Platelet-derived growth factor receptor |
PD-L1 | Programmed death-ligand 1 |
PI3K | phosphatidylinositol-3 kinase |
pp-GalNAc-T6 | UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-6 |
PSCs | Pancreatic Stellate Cells |
RAF | rapidly accelerated fibrosarcoma |
RANTES | Regulated on Activation, Normal T Cell Expressed and Secreted |
R-SMAD | receptor-regulated SMAD |
R0 | resections: no cancer cells present microscopically at the primary tumor site |
ROS | Reactive Oxygen Species |
Saa3 | Serum Amyloid A 3 |
SBE | SMAD Binding Element |
SHH | Sonic Hedgehog |
SMAD | Small Mother Against Decapentaplegic |
TAMs | Tumour-Associated Macrophages |
TCA | Tricarboxylic Acid |
TET | ten-eleven translocation methylcytosine dioxygenases |
TEXs | Tumor-Derived Exosomes |
TGF-β | Transforming Growth Factor β |
TGFβR | Transforming Growth Factor β Receptor |
TLR | Toll-Like Receptor |
TME | Tumour Microenvironment |
TNF-α | Tumor Necrosis Factor alpha |
TP53 | Tumour Protein 53 |
T-reg | Regulatory T Lymphocytes |
VEGF | Vascular Endothelial Growth Factor |
YAP | Yes-associated protein |
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Mercanti, L.; Sindaco, M.; Mazzone, M.; Di Marcantonio, M.C.; Piscione, M.; Muraro, R.; Mincione, G. PDAC, the Influencer Cancer: Cross-Talk with Tumor Microenvironment and Connected Potential Therapy Strategies. Cancers 2023, 15, 2923. https://doi.org/10.3390/cancers15112923
Mercanti L, Sindaco M, Mazzone M, Di Marcantonio MC, Piscione M, Muraro R, Mincione G. PDAC, the Influencer Cancer: Cross-Talk with Tumor Microenvironment and Connected Potential Therapy Strategies. Cancers. 2023; 15(11):2923. https://doi.org/10.3390/cancers15112923
Chicago/Turabian StyleMercanti, Leonardo, Maria Sindaco, Mariangela Mazzone, Maria Carmela Di Marcantonio, Mariagrazia Piscione, Raffaella Muraro, and Gabriella Mincione. 2023. "PDAC, the Influencer Cancer: Cross-Talk with Tumor Microenvironment and Connected Potential Therapy Strategies" Cancers 15, no. 11: 2923. https://doi.org/10.3390/cancers15112923