Identifiers
HUGO:TGFB1 HUGO:TGFB2 HUGO:TGFB3
Maps_Modules
MODULE:INPUT_INHIBITORS MODULE:IMMUNE_SUPPRESSION MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:EFFECTOR_INHIBITION MODULE:TUMOR_GROWTH MODULE:GROWTH_FACTORS_EXPRESSION
References
MACROPHAGE
MDSC
NATURAL_KILLER
DENDRITIC_CELL
MAST_CELL
NEUTROPHIL
CASCADE:TGFB
CASCADE:STING
CASCADE:STAB2
CASCADE:TLR2_4
CASCADE:IFNG
PMID:24132110
TGFB has been identified as a factor that inhibits the functional maturation of this cell population9. Immature NK cells do not respond to foreign antigens, thus exposure of NK cells to TGFβ will impair the recognition and the clearance of tumour cells. The inhibition of maturation also prevents the systemic effects of NK cells,
for example, activation of antigen-presenting dendritic cells and inhibition of interferon-γ (IFNγ) secretion, which drives T helper 1 cell (TH1 cell) maturation
TGFB1, TGFB2, TGFB3 ligands bind to the type 2 TGFβ receptor (TGFBR2), which causes recruitment and phosphorylation of TGFBR1, resulting in downstream signalling activation.
PMID:17070508, PMID:18490733
TGFB downregulates NKG2D expression.
IL-2/IL-18 prevent the down-modulation of NKG2D by TGF-β in NK cells via the c-Jun N-terminal kinase (JNK) pathway
PMID:2871107
Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness.
PMID:20538542
TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression.
The roles of TGFβ in the tumour microenvironment.
PMID:20616810
The polarization of immune cells in the tumour environment by TGFbeta.
PMID:22703233
TGFB1 participates in M2 activation.
PMID:7594497
TGFB1 upregulates IL10 expression in macrophages.
TGFB1 and IL10 dowregulate expression of TNF.
PMID:21278795
TGFB-induced IRAK3 (IRAK-M) expression in tumor-associated macrophages
and inhibit TLR-dependent signaling
PMID:20644162
Cytokine-induced CD33+ human MDSCs have upregulated iNOS, TGFβ, VEGF.
PMID:19109155
MDSC inhibit cytotoxicity, NKG2D expression, and IFN-gamma production of NK cells both in vitro and in vivo.
Membrane-bound TGF-beta1 on MDSC is responsible for MDSC-mediated suppression of NK cells.
PMID:21372296
HMGB1 induces the production of angiogenic factors VEGF, and TGFB1 by macrophage via TLR4-dependent mechanisms.
PMID:16424049
IFNG induces INOS and IL10 expression and TGFB secretion in MDSC
PMID:15099563
Mast cells produce cytokines TNF-a, TGF-b, IFN-a, IL-1a, IL-1b, IL-5, IL-6,
IL-13, IL-16, IL-18
PMID:26966341
tudies have shown that, analogously to the M1 and M2 dichotomy, TANs develop a protumorigenic (N2) phenotype in untreated tumors, largely driven by the presence of TGF-β
→ TGFB*@default
→ TGFB*@INNATE_IMMUNE_CELL_Membrane
→ TUMOR_GROWTH@TUMOR_CELL_AS_EFFECTOR
→ TGFB*@INNATE_IMMUNE_CELL_Cytosol
→ TGFB*@INNATE_IMMUNE_CELL_Cytosol
→ TGFB*@INNATE_IMMUNE_CELL_Cytosol
→ IMMUNE_SUPRESSION@default
+ TGFBR2@INNATE_IMMUNE_CELL_Membrane + TGFB*@default → TGFB*:TGFBR1:TGFBR2@INNATE_IMMUNE_CELL_Membrane
→ THBS1@default
→ rTNF@INNATE_IMMUNE_CELL_Cytosol
→ arMIR183@INNATE_IMMUNE_CELL_Cytosol
→ rCCL5@INNATE_IMMUNE_CELL_Cytosol
→ rNKG2D*@INNATE_IMMUNE_CELL_Cytosol
→ rNKp30*@INNATE_IMMUNE_CELL_Cytosol
→ SMAD3|pho@INNATE_IMMUNE_CELL_Cytosol
→ arMIR1245A@INNATE_IMMUNE_CELL_Cytosol
→ arMIR185@INNATE_IMMUNE_CELL_Cytosol
→ SMAD2|pho@INNATE_IMMUNE_CELL_Cytosol
→ rIL10@INNATE_IMMUNE_CELL_Cytosol
→ O_sub_2_endsub__super_-_endsuper_@INNATE_IMMUNE_CELL_Cytosol
→ rCCL3@INNATE_IMMUNE_CELL_Cytosol
→ rCCL2@INNATE_IMMUNE_CELL_Cytosol
→ rIRAK3@INNATE_IMMUNE_CELL_Cytosol