Table 1.
Tumorigenic effect of the relationship between stromal cells and immune cells in TME.
| Cell type | Mediator | Effect function | Type of Tumor | Ref. |
|---|---|---|---|---|
|
CAFs
TEC CAA |
MCP-1, SDF-1 production → IL-10↑, IL-12↓ | Monocyte recruitment M2-like macrophage differentiation |
Breast cancer | (45) |
| IL-6, SDF-1 production | M2 macrophage differentiation | Prostate cancer | (50) | |
| CCL-2 (MCP-1) production → CCR2A/2B pathway activation |
Monocyte recruitment for TAM differentiation | Breast cancer | (51, 52) | |
| IL-6/STAT3 pathway activation | Promotion of MDSC differentiation | Pancreatic cancer | (61) | |
| IL-6/STAT3 activation → IDO production↑ | Induction of DC cell | Hepatocellular carcinoma | (66) | |
| IL-6, STAT3, PD-L1 signaling pathway | Activation of neutrophil Impairment of T cell function |
Hepatocellular carcinoma | (67) | |
| IL-6, GM-CSF production | Induction of TAM infiltration | Colon cancer | (68) | |
| IL-6, IL-8 production | Attraction of monocyte recruitment for TAM differentiation, NK cell function inhibition |
Colorectal cancer | (70) | |
| TGF-β production → IL-4↑, IL-10↑, IL-12↓ → PD-L1, HLA-DR↑ | M2 macrophage polarization | Hepatocellular carcinoma | (78, 79) | |
| PD-L2, FASL engagement↑ | Induction of CD8+ T cell death | Lung cancer | (81) | |
| CXCL12 (SDF-1)-CXCR4 expression | CD4+CD25+ T cell proliferation | Breast cancer | (82–84) | |
| CXCL12 → via B7H3, CD73, DPP4↑ | Attraction of CD4+CD25+ T cell, Increase T cell survival, differentiation |
|||
| PD-L1(B7H1), B7DC expression IL-6, CXCL8, TNF, TGFB1, VEGFA↑ |
Induction of T cell apoptosis and FOXP3+ Treg proliferation | Head and neck squamous cancer | (85) | |
| PGE2 production → inhibition of NK receptor (NKp44, NKp30), perforins, granzymes | Inhibition of NK cell function | Melanoma | (99, 100) | |
| PGE2 expression, IDO production | Suppression of NK cell activation | Hepatocellular carcinoma | (101, 102) | |
| Notch1-induced VCAM1 expression | Promotion of Neutrophil infiltration | Ovarian, Lung carcinoma, melanoma | (110) | |
| FasL production → Fas/FasL death signaling activation | Suppression of CD8+ T cell | Glioma | (111) | |
| TGF-β, IL-10 production, via PD1/PD-L1 pathway |
Attenuation of CD8+ T cell function | Melanoma | (112) | |
| CLEVER-1/stabilin-1 production | FOXP3+ Treg recruitment | Hepatocellular carcinoma | (114) | |
| CCL-2 production → IL-1β/CXCL12 activation | Induction of macrophage recruitment | Breast cancer | (117) | |
| PD-L1 expression | Inhibition of CD8+ T cells | Breast cancer | (120) | |
| IL-8 production | Induction of Neutrophil recruitment | Pancreatic ductal adenocarcinoma | (122) | |
| MSC | TGF-β production | Induction of Treg cell | Breast cancer | (125) |
| SDF-1/CXCR7 axis | Induction of Breg cell | Non-cancerous | (126) | |
| TNF-α production → induction PD-L1↑ | Suppression of CD8+ T cell | Colon cancer | (131) | |
| Neutrophil | IL-1β production → MMP-9 activation | EC activation → metastasis ability↑ | Pancreatic ductal adenocarcinoma | (132–134) |
|
Monocyte/
Macrophage |
OPN production | CAF proliferation → promoting malignancy↑ |
Hepatocellular carcinoma | (141) |
| Wnt7a expression → Wnt/β-catenin signaling | Myofibroblasts differentiation of MSC → fibrosis↑ | Non-cancer (Pulmonary fibrosis) |
(144) | |
| miR-155-5p, 221-5p in MDE | TEC proliferation → promoting growth↑ |
Pancreatic ductal adenocarcinoma | (147, 148) | |
| NK cell | VEGF, PIGF production | HUVECs migration, formation↑ → tumor growth↑, angiogenesis↑ |
Non-small cell lung cancer | (150) |
| Mast cell | TGF-β production | Myofibroblasts differentiation induction, proliferation↑ | Neurofibromas | (154) |
| Tryptase production | Promoting the transformation of prostate ECs morphology | Prostate cancer | (155) | |
| IL-13, Tryptase production | Stimulation of PSC proliferation | Pancreatic ductal adenocarcinoma | (156) |
CAFs, Cancer-associated fibroblasts; TECs, Tumor-endothelial cells; CAAs, Cancer-associated adipocytes; PSC, Pancreatic stellate cell; TAN, Tumor-associated neutrophil; CM, Conditioned medium; EC, Endothelial cells; FasL, Fibroblast associated ligand; OPN, Osteopontin; MDE, Macrophage-derived exosomes; VEGF, Vascular endothelial growth factor; PIGF, Placental growth factor; HUVEC, Human umbilical vein endothelial cells.
↑, increase; ↓, decrease.