Table 3.
Contribution of protumor TME components in PC.
| TME Components | Biological Mechanisms | Implication in PC | Ref. | ||
|---|---|---|---|---|---|
| Cellular | Stromal cells | aPSC | ↑tumor proliferation, ECM production, EMT, proangiogenic soluble factors secretion; ↓CD8+ T cells migration |
↑chemoresistance; ↑antitumor immune response |
[67,68,69,70] |
| CAF | ↑tumor proliferation, production of proangiogenic soluble factors, M2 polarization | ↑chemoresistance; ↓OS |
[71,72,73] | ||
| Endothelial | ↑antitumor immune cells | ↑OS | [74] | ||
| Immune cells | M2 | ↑Snail, vimentin and EMT; ↓E-cadherin |
↓patient prognosis | [75,76] | |
| Neutrophils | ↓immunoresponse | ↑chemoresistance | [77] | ||
| CD4+/CD25+/Foxp3+ Treg | ↑immunosuppressive TME; ↓antitumor immune cells |
↑TNM stage | [78,79] | ||
| MDSC | ↑immunosuppressive TME | ↑tumor growth invasion and angiogenesis | [80,81,82] | ||
| Acellular | ECM | Collagen I, IV, V | ↑tumor proliferation and EMT | ↓patient prognosis | [83,84,85,86,87] |
| Lumican | ↑tumor proliferation | ↓patient prognosis | [88] | ||
| Fibronectin | ↑EMT | ↓patient prognosis and OS; ↑chemoresistance |
[69,89] | ||
| Cytokines | IL-1β | ↑inflammation, migration | ↑chemoresistance; ↓PFS |
[90,91] | |
| IL-6 | ↑tumor proliferation, angiogenesis, EMT and immunosuppressive TME | ↓patient prognosis | [92,93,94] | ||
| IL-8 | ↑tumor proliferation, angiogenesis, CSC properties, ECM disruption and migration | ↓patient prognosis | [95,96,97] | ||
| MIF | ↑cell proliferation and EMT | ↑chemoresistance; ↓OS |
[98,99] | ||
| IL-10 | ↓CD4+ T-cell response | ↓OS | [100,101,102] | ||
| TGF-β | ↑EMT; ↓CD8+ T-cell apoptosis |
↓OS | [103,104,105,106] | ||
| TNF-α | ↑tumor proliferation, EMT and migration | ↓patient prognosis | [107,108] | ||
aPSC, activated pancreatic stellate cells; CAF, cancer associated fibroblasts; CSC, cancer stem cells; DC, dendritic cells; ECM, extracellular matrix; EMT, epithelial mesenchymal transition; IL, interleukin; M2, macrophages M2 phenotype; MDSC, myeloid-derived suppressor cells; MIF, macrophage migration inhibitor factor; TGF, transforming growth factor; TNF, tumor necrosis factor; TNM, tumor node metastasis; OS, overall survival; PFS, progression free survival.