Fig. 2

Effects of FGFR signaling on the TME. a.| FGF/FGFR promotes PD-1 expression and reduces IFNy and GZMB secretion by effector T cells, resulting in a decrease in anti-tumor immunity of T-cells. b.| FGF/FGFR promotes Treg cell survival by assisting IL-2-mediated STAT5 phosphorylation. FGF also promotes the M2-type polarization of TAMs. These functions of FGF/FGFR enhance immunosuppressive effects. c.| FGF/FGFR signaling directly inhibits MHC II expression via the RAS/MAPK pathway. At the same time, FGF/FGFR signaling also inhibited interferon-mediated expression of MHC I and PD-L1 and secretion of CXCL10 via SOSC1. In addition, FGF/FGFR signaling promotes PD-L1 expression through the JAK/STAT pathway and initiates PD-L1 transcription through the upregulation of YAP. d.| On the one hand, FGFR4 reduces PD-L1 degradation by promoting GSK3β phosphorylation at the Ser 9 site. On the other hand, FGFR1 promotes the degradation of ubiquitinated PD-L1 by promoting NEDD4 phosphorylation. IFN-y, interferon-γ; GZMB, granzyme B; TAM, tumor-associated macrophage; MHC, major histocompatibility complex; PD-L1, SOSC1, suppressor of cytokine signaling 1; GSK3β, glycogen synthase kinase 3 beta