Table 3.
Mediators (soluble mediators or exosomes) of the induction of EMT by cells of the immune system.
| Mediator | Summary of Experimental Observations. | References |
|---|---|---|
| Cytokines | ||
| IFN-γ | IFN-γ and other cytokines mediated NK cell-induced increased malignancy of melanoma cells; | [40,61,80,81] |
| IFN-γ mediated NK cell-induced EMT and HCC formation in hepatocytes from HBsAg transgenic mice; | ||
| IFN-γ induced EMT in prostate and papillary thyroid cancer cells. | ||
| TNF-α | TNF-α and other cytokines mediated NK cell-induced increased malignancy of melanoma cells; | [40,75,81,82,83,84] |
| TNF-α, with other cytokines, induced EMT in IBC cells in a manner similar to soluble factors from activated T cells; | ||
| TNF-α induced EMT in papillary thyroid cancer and HCC cells; | ||
| TNF-α induced EMT in HCC cells, with synergistic induction in combination with IL-1β and IL-6; | ||
| TNF-α derived from macrophages induced tumor cell EMT. | ||
| TGF-β | TGF-β induced HLA class I downregulation and EMT in prostate cancer cells; | [21,62,66,70,73,75,95] |
| TGF-β mediated, with other cytokines, EMT-like changes induced by MDSCs in melanoma cells; | ||
| TGF-β mediated EMT of HCCs induced by TAMs; | ||
| TGF-β was the main mediator of EMT induced in teratocarcinoma cells by macrophage-conditioned medium; | ||
| TGF-β mediated EMT in lung adenocarcinoma cells induced by polymorphonuclear neutrophils; | ||
| TGF-β, with other cytokines, induced EMT in IBC cells in a manner similar to soluble factors from activated T cells; | ||
| TGF-β induced EMT in lung adenocarcinoma cells, with synergistic effects with other cytokines from a macrophage cell line. | ||
| EGF | EGF induced HLA-I downregulation and EMT in prostate cancer cells; | [21,62,89] |
| EGF mediated, with other cytokines, EMT-like changes induced by MDSCs in melanoma cells; | ||
| EGF induced EMT and enhanced the migration of ovarian carcinoma cells. | ||
| HGF | HGF mediated, with other cytokines, EMT-like changes induced by MDSCs in melanoma cells. | [62] |
| IL-6 | IL-6, with other cytokines, induced EMT in IBC cells in a manner similar to soluble factors from activated T cells; | [75,76,85,86,87,88,89,90] |
| IL-6 from activated T cells induced EMT in premalignant pancreatic cells; | ||
| IL-6 induced EMT in breast cancer, CRC, NSCLC, cervical carcinoma, and ovarian carcinoma cells; | ||
| IL-17 | IL-6 induced EMT in prostate cancer cell lines. | [92,93] |
| IL-17 induced EMT and enhanced migration and invasion in nasopharyngeal carcinoma cell lines. | ||
| IL-18 | IL-18 induced EMT in lung adenocarcinoma cells. | [94] |
| HMGB1 | HMGB1 induced EMT in CRC cells. | [96] |
| MIF | MIF induced EMT in pancreatic cancer cells. | [97] |
| BAF | BAF induced EMT in pancreatic cancer cells. | [78] |
| Chemokines | ||
| IL-8 | IL-8 mediated mast cell-induced EMT in human thyroid cancer cells; | [57,67,91,98] |
| IL-8 mediated macrophage-induced EMT in HCC cells; | ||
| IL-8 induced EMT and migration in human ovarian cancer cells; | ||
| review of IL-8 as a mediator between inflammation and tumor cell EMT. | ||
| CCL2 | CCL2 enhanced IL-6 induced EMT and invasion of NSCLC cells. | [87] |
| CCL18 | CCL18 from TAM induced EMT in breast cancer cells; | [51,99] |
| CCL18 induced EMT and the invasion and migration of pancreatic cancer cells. | ||
| CCL21 | CCL21 induced EMT and metastasis in CD133+ pancreatic cancer CSCs. | [100] |
| Exosomes | ||
| Exosomes from TILs induced EMT in human esophageal squamous cell carcinoma cells. | [74] | |
Abbreviations: BAF, B-cell activating factor; CCL, C-C motif chemokine ligand; CRC, colorectal carcinoma; CSC, cancer stem-like cell; EMT, epithelial-mesenchymal transition; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; HGF, hepatocyte growth factor; HLA, human leukocyte antigen; HMGB, high-mobility group box; IBC, inflammatory breast cancer; IFN, interferon; IL, interleukin; MDSC, myeloid-derived suppressor cell; MIF, macrophage migration inhibitory factor; NK, natural killer; NSCLC, non-small cell lung cancer; TAM, tumor-associated macrophage; TGF, transforming growth factor; TIL, tumor-infiltrating lymphocyte; TNF, tumor necrosis factor.