Table 1 Effects of FGF/FGFR signaling on cells in tumor microenvironment
Cell of TME | Trigger signal | Mechanism | Effect |
|---|---|---|---|
T-cell | The expression of PD-1, CTLA-4 and TIM-3 in T-cells was up-regulated | T-cell Exhaustion↑ | |
bFGF + VEGFA [22], VEGFR + FGFR [62], FGFR [63], FGFR1 [59], FGFR3 [20, 55], FGFR4 [24] | Inhibit the production of IFN-γ and GZMB | T-cell infiltration↓ | |
FGFR3 [66] | Upward PPARG signal | ||
Indirectly inhibited the recruitment of CD8 + T- cells via CXCL16 | |||
Promote IL-2 production by activating NF-κB | T-cell infiltration↑ | ||
Tumor-cell | The expression of PD-L1 in tumors was up-regulated | Immune escape↑ | |
Inhibit the expression of MHC I and MHC II molecules in tumor cells | |||
FGFR3 [25] | Promote PD-L1 degradation in tumor cells | Immune escape↓ | |
Macrophage | FGFR1 [19] | Promote macrophage recruitment through induction of CX3CL1 expression | Immunosuppression↑ |
FGF2 [45] | Promote M2-type polarization of macrophages | ||
Treg-cell | FGFR4 [24] | Promote the differentiation and survival of Treg cells by regulating IL-2 | |
Epithelial-cell | The FGF2-FGFR1/2IIIc signaling axis promotes cellular EMT | EMT↑ | |
FGF signal inhibits EMT by blocking TGF-β | EMT↓ | ||
Endothelial-cell | FGF2-FGFR [17] | Enhance endothelial cell chemotaxis by regulating MAPK signaling | Endothelial migration and generation ↑ |
FGF [155] | Promote extracellular matrix degradation by stimulating the shedding of MMP2 and MMP9 | ||
FGF2/FGFR1 [18] | Control endothelial cell energy metabolism by inducing HK2 expression | ||
FGF [152] | Involved in inhibiting the expression of endothelial cell adhesion molecules | T-cell homing and recruitment↓ |