Browse TNF

Summary
SymbolTNF
Nametumor necrosis factor
Aliases TNFSF2; DIF; TNF-alpha; TNF superfamily, member 2; TNFA; tumor necrosis factor (TNF superfamily, member 2); ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane Single-pass type II membrane protein ; SUBCELLULAR LOCATION: Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein.; SUBCELLULAR LOCATION: Tumor necrosis factor, soluble form: Secreted.; SUBCELLULAR LOCATION: C-domain 1: Secreted.; SUBCELLULAR LOCATION: C-domain 2: Secreted.
Domain PF00229 TNF(Tumour Necrosis Factor) family
Function

Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918). ; FUNCTION: The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.

> Gene Ontology
 
Biological Process GO:0000060 protein import into nucleus, translocation
GO:0000185 activation of MAPKKK activity
GO:0000187 activation of MAPK activity
GO:0000302 response to reactive oxygen species
GO:0000303 response to superoxide
GO:0000305 response to oxygen radical
GO:0001101 response to acid chemical
GO:0001503 ossification
GO:0001649 osteoblast differentiation
GO:0001659 temperature homeostasis
GO:0001660 fever generation
GO:0001763 morphogenesis of a branching structure
GO:0001818 negative regulation of cytokine production
GO:0001819 positive regulation of cytokine production
GO:0001885 endothelial cell development
GO:0001942 hair follicle development
GO:0001959 regulation of cytokine-mediated signaling pathway
GO:0002064 epithelial cell development
GO:0002237 response to molecule of bacterial origin
GO:0002250 adaptive immune response
GO:0002367 cytokine production involved in immune response
GO:0002374 cytokine secretion involved in immune response
GO:0002377 immunoglobulin production
GO:0002437 inflammatory response to antigenic stimulus
GO:0002439 chronic inflammatory response to antigenic stimulus
GO:0002440 production of molecular mediator of immune response
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002455 humoral immune response mediated by circulating immunoglobulin
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002521 leukocyte differentiation
GO:0002526 acute inflammatory response
GO:0002544 chronic inflammatory response
GO:0002573 myeloid leukocyte differentiation
GO:0002637 regulation of immunoglobulin production
GO:0002673 regulation of acute inflammatory response
GO:0002675 positive regulation of acute inflammatory response
GO:0002676 regulation of chronic inflammatory response
GO:0002678 positive regulation of chronic inflammatory response
GO:0002683 negative regulation of immune system process
GO:0002685 regulation of leukocyte migration
GO:0002687 positive regulation of leukocyte migration
GO:0002697 regulation of immune effector process
GO:0002698 negative regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002700 regulation of production of molecular mediator of immune response
GO:0002701 negative regulation of production of molecular mediator of immune response
GO:0002703 regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002706 regulation of lymphocyte mediated immunity
GO:0002708 positive regulation of lymphocyte mediated immunity
GO:0002712 regulation of B cell mediated immunity
GO:0002714 positive regulation of B cell mediated immunity
GO:0002718 regulation of cytokine production involved in immune response
GO:0002719 negative regulation of cytokine production involved in immune response
GO:0002739 regulation of cytokine secretion involved in immune response
GO:0002740 negative regulation of cytokine secretion involved in immune response
GO:0002761 regulation of myeloid leukocyte differentiation
GO:0002763 positive regulation of myeloid leukocyte differentiation
GO:0002790 peptide secretion
GO:0002791 regulation of peptide secretion
GO:0002819 regulation of adaptive immune response
GO:0002821 positive regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002861 regulation of inflammatory response to antigenic stimulus
GO:0002863 positive regulation of inflammatory response to antigenic stimulus
GO:0002874 regulation of chronic inflammatory response to antigenic stimulus
GO:0002876 positive regulation of chronic inflammatory response to antigenic stimulus
GO:0002889 regulation of immunoglobulin mediated immune response
GO:0002891 positive regulation of immunoglobulin mediated immune response
GO:0002920 regulation of humoral immune response
GO:0002922 positive regulation of humoral immune response
GO:0002923 regulation of humoral immune response mediated by circulating immunoglobulin
GO:0002925 positive regulation of humoral immune response mediated by circulating immunoglobulin
GO:0003158 endothelium development
GO:0005996 monosaccharide metabolic process
GO:0006006 glucose metabolic process
GO:0006066 alcohol metabolic process
GO:0006413 translational initiation
GO:0006417 regulation of translation
GO:0006446 regulation of translational initiation
GO:0006447 regulation of translational initiation by iron
GO:0006470 protein dephosphorylation
GO:0006509 membrane protein ectodomain proteolysis
GO:0006606 protein import into nucleus
GO:0006643 membrane lipid metabolic process
GO:0006665 sphingolipid metabolic process
GO:0006672 ceramide metabolic process
GO:0006694 steroid biosynthetic process
GO:0006766 vitamin metabolic process
GO:0006775 fat-soluble vitamin metabolic process
GO:0006801 superoxide metabolic process
GO:0006809 nitric oxide biosynthetic process
GO:0006909 phagocytosis
GO:0006913 nucleocytoplasmic transport
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006953 acute-phase response
GO:0006959 humoral immune response
GO:0006970 response to osmotic stress
GO:0006979 response to oxidative stress
GO:0007009 plasma membrane organization
GO:0007043 cell-cell junction assembly
GO:0007159 leukocyte cell-cell adhesion
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007254 JNK cascade
GO:0007431 salivary gland development
GO:0007435 salivary gland morphogenesis
GO:0008202 steroid metabolic process
GO:0008544 epidermis development
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0008643 carbohydrate transport
GO:0008645 hexose transport
GO:0009110 vitamin biosynthetic process
GO:0009306 protein secretion
GO:0009615 response to virus
GO:0009636 response to toxic substance
GO:0009651 response to salt stress
GO:0009894 regulation of catabolic process
GO:0009895 negative regulation of catabolic process
GO:0009896 positive regulation of catabolic process
GO:0009914 hormone transport
GO:0010035 response to inorganic substance
GO:0010608 posttranscriptional regulation of gene expression
GO:0010692 regulation of alkaline phosphatase activity
GO:0010693 negative regulation of alkaline phosphatase activity
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
GO:0010817 regulation of hormone levels
GO:0010827 regulation of glucose transport
GO:0010829 negative regulation of glucose transport
GO:0010876 lipid localization
GO:0010883 regulation of lipid storage
GO:0010888 negative regulation of lipid storage
GO:0010893 positive regulation of steroid biosynthetic process
GO:0010921 regulation of phosphatase activity
GO:0010923 negative regulation of phosphatase activity
GO:0010950 positive regulation of endopeptidase activity
GO:0010952 positive regulation of peptidase activity
GO:0015749 monosaccharide transport
GO:0015758 glucose transport
GO:0015833 peptide transport
GO:0016042 lipid catabolic process
GO:0016064 immunoglobulin mediated immune response
GO:0016311 dephosphorylation
GO:0017038 protein import
GO:0018105 peptidyl-serine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0019058 viral life cycle
GO:0019079 viral genome replication
GO:0019216 regulation of lipid metabolic process
GO:0019218 regulation of steroid metabolic process
GO:0019318 hexose metabolic process
GO:0019430 removal of superoxide radicals
GO:0019724 B cell mediated immunity
GO:0019915 lipid storage
GO:0022404 molting cycle process
GO:0022405 hair cycle process
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0022612 gland morphogenesis
GO:0023061 signal release
GO:0030072 peptide hormone secretion
GO:0030073 insulin secretion
GO:0030099 myeloid cell differentiation
GO:0030100 regulation of endocytosis
GO:0030148 sphingolipid biosynthetic process
GO:0030198 extracellular matrix organization
GO:0030278 regulation of ossification
GO:0030279 negative regulation of ossification
GO:0030316 osteoclast differentiation
GO:0030323 respiratory tube development
GO:0030324 lung development
GO:0030335 positive regulation of cell migration
GO:0030656 regulation of vitamin metabolic process
GO:0030730 sequestering of triglyceride
GO:0030856 regulation of epithelial cell differentiation
GO:0030865 cortical cytoskeleton organization
GO:0030866 cortical actin cytoskeleton organization
GO:0031098 stress-activated protein kinase signaling cascade
GO:0031329 regulation of cellular catabolic process
GO:0031331 positive regulation of cellular catabolic process
GO:0031334 positive regulation of protein complex assembly
GO:0031349 positive regulation of defense response
GO:0031503 protein complex localization
GO:0031620 regulation of fever generation
GO:0031622 positive regulation of fever generation
GO:0031649 heat generation
GO:0031650 regulation of heat generation
GO:0031652 positive regulation of heat generation
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0031960 response to corticosteroid
GO:0032103 positive regulation of response to external stimulus
GO:0032147 activation of protein kinase activity
GO:0032386 regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032496 response to lipopolysaccharide
GO:0032515 negative regulation of phosphoprotein phosphatase activity
GO:0032602 chemokine production
GO:0032609 interferon-gamma production
GO:0032635 interleukin-6 production
GO:0032637 interleukin-8 production
GO:0032642 regulation of chemokine production
GO:0032649 regulation of interferon-gamma production
GO:0032675 regulation of interleukin-6 production
GO:0032677 regulation of interleukin-8 production
GO:0032715 negative regulation of interleukin-6 production
GO:0032722 positive regulation of chemokine production
GO:0032729 positive regulation of interferon-gamma production
GO:0032755 positive regulation of interleukin-6 production
GO:0032757 positive regulation of interleukin-8 production
GO:0032768 regulation of monooxygenase activity
GO:0032770 positive regulation of monooxygenase activity
GO:0032800 receptor biosynthetic process
GO:0032844 regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0032872 regulation of stress-activated MAPK cascade
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0032984 macromolecular complex disassembly
GO:0033002 muscle cell proliferation
GO:0033135 regulation of peptidyl-serine phosphorylation
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033157 regulation of intracellular protein transport
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0033619 membrane protein proteolysis
GO:0033674 positive regulation of kinase activity
GO:0034113 heterotypic cell-cell adhesion
GO:0034114 regulation of heterotypic cell-cell adhesion
GO:0034116 positive regulation of heterotypic cell-cell adhesion
GO:0034248 regulation of cellular amide metabolic process
GO:0034250 positive regulation of cellular amide metabolic process
GO:0034329 cell junction assembly
GO:0034330 cell junction organization
GO:0034394 protein localization to cell surface
GO:0034504 protein localization to nucleus
GO:0034599 cellular response to oxidative stress
GO:0034612 response to tumor necrosis factor
GO:0034614 cellular response to reactive oxygen species
GO:0035094 response to nicotine
GO:0035239 tube morphogenesis
GO:0035272 exocrine system development
GO:0035303 regulation of dephosphorylation
GO:0035304 regulation of protein dephosphorylation
GO:0035305 negative regulation of dephosphorylation
GO:0035308 negative regulation of protein dephosphorylation
GO:0035507 regulation of myosin-light-chain-phosphatase activity
GO:0035509 negative regulation of myosin-light-chain-phosphatase activity
GO:0038034 signal transduction in absence of ligand
GO:0038061 NIK/NF-kappaB signaling
GO:0040017 positive regulation of locomotion
GO:0042033 chemokine biosynthetic process
GO:0042035 regulation of cytokine biosynthetic process
GO:0042089 cytokine biosynthetic process
GO:0042107 cytokine metabolic process
GO:0042108 positive regulation of cytokine biosynthetic process
GO:0042176 regulation of protein catabolic process
GO:0042228 interleukin-8 biosynthetic process
GO:0042303 molting cycle
GO:0042306 regulation of protein import into nucleus
GO:0042307 positive regulation of protein import into nucleus
GO:0042345 regulation of NF-kappaB import into nucleus
GO:0042346 positive regulation of NF-kappaB import into nucleus
GO:0042348 NF-kappaB import into nucleus
GO:0042359 vitamin D metabolic process
GO:0042362 fat-soluble vitamin biosynthetic process
GO:0042368 vitamin D biosynthetic process
GO:0042633 hair cycle
GO:0042634 regulation of hair cycle
GO:0042635 positive regulation of hair cycle
GO:0042692 muscle cell differentiation
GO:0042742 defense response to bacterium
GO:0042886 amide transport
GO:0042990 regulation of transcription factor import into nucleus
GO:0042991 transcription factor import into nucleus
GO:0042993 positive regulation of transcription factor import into nucleus
GO:0043062 extracellular structure organization
GO:0043112 receptor metabolic process
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043200 response to amino acid
GO:0043241 protein complex disassembly
GO:0043242 negative regulation of protein complex disassembly
GO:0043243 positive regulation of protein complex disassembly
GO:0043244 regulation of protein complex disassembly
GO:0043254 regulation of protein complex assembly
GO:0043279 response to alkaloid
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043297 apical junction assembly
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043491 protein kinase B signaling
GO:0043506 regulation of JUN kinase activity
GO:0043507 positive regulation of JUN kinase activity
GO:0043588 skin development
GO:0043666 regulation of phosphoprotein phosphatase activity
GO:0043900 regulation of multi-organism process
GO:0043901 negative regulation of multi-organism process
GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism
GO:0044089 positive regulation of cellular component biogenesis
GO:0044110 growth involved in symbiotic interaction
GO:0044116 growth of symbiont involved in interaction with host
GO:0044117 growth of symbiont in host
GO:0044126 regulation of growth of symbiont in host
GO:0044130 negative regulation of growth of symbiont in host
GO:0044144 modulation of growth of symbiont involved in interaction with host
GO:0044146 negative regulation of growth of symbiont involved in interaction with host
GO:0044283 small molecule biosynthetic process
GO:0044723 single-organism carbohydrate metabolic process
GO:0044744 protein targeting to nucleus
GO:0045069 regulation of viral genome replication
GO:0045071 negative regulation of viral genome replication
GO:0045073 regulation of chemokine biosynthetic process
GO:0045080 positive regulation of chemokine biosynthetic process
GO:0045123 cellular extravasation
GO:0045216 cell-cell junction organization
GO:0045414 regulation of interleukin-8 biosynthetic process
GO:0045416 positive regulation of interleukin-8 biosynthetic process
GO:0045428 regulation of nitric oxide biosynthetic process
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045444 fat cell differentiation
GO:0045445 myoblast differentiation
GO:0045446 endothelial cell differentiation
GO:0045598 regulation of fat cell differentiation
GO:0045599 negative regulation of fat cell differentiation
GO:0045601 regulation of endothelial cell differentiation
GO:0045637 regulation of myeloid cell differentiation
GO:0045639 positive regulation of myeloid cell differentiation
GO:0045661 regulation of myoblast differentiation
GO:0045662 negative regulation of myoblast differentiation
GO:0045667 regulation of osteoblast differentiation
GO:0045668 negative regulation of osteoblast differentiation
GO:0045670 regulation of osteoclast differentiation
GO:0045672 positive regulation of osteoclast differentiation
GO:0045682 regulation of epidermis development
GO:0045684 positive regulation of epidermis development
GO:0045727 positive regulation of translation
GO:0045732 positive regulation of protein catabolic process
GO:0045785 positive regulation of cell adhesion
GO:0045807 positive regulation of endocytosis
GO:0045833 negative regulation of lipid metabolic process
GO:0045834 positive regulation of lipid metabolic process
GO:0045860 positive regulation of protein kinase activity
GO:0045862 positive regulation of proteolysis
GO:0045926 negative regulation of growth
GO:0045940 positive regulation of steroid metabolic process
GO:0045948 positive regulation of translational initiation
GO:0045994 positive regulation of translational initiation by iron
GO:0046136 positive regulation of vitamin metabolic process
GO:0046165 alcohol biosynthetic process
GO:0046209 nitric oxide metabolic process
GO:0046323 glucose import
GO:0046324 regulation of glucose import
GO:0046325 negative regulation of glucose import
GO:0046328 regulation of JNK cascade
GO:0046330 positive regulation of JNK cascade
GO:0046467 membrane lipid biosynthetic process
GO:0046513 ceramide biosynthetic process
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046824 positive regulation of nucleocytoplasmic transport
GO:0046879 hormone secretion
GO:0046883 regulation of hormone secretion
GO:0046889 positive regulation of lipid biosynthetic process
GO:0046890 regulation of lipid biosynthetic process
GO:0048305 immunoglobulin secretion
GO:0048525 negative regulation of viral process
GO:0048545 response to steroid hormone
GO:0048565 digestive tract development
GO:0048566 embryonic digestive tract development
GO:0048568 embryonic organ development
GO:0048659 smooth muscle cell proliferation
GO:0048660 regulation of smooth muscle cell proliferation
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0048732 gland development
GO:0048754 branching morphogenesis of an epithelial tube
GO:0048871 multicellular organismal homeostasis
GO:0050663 cytokine secretion
GO:0050673 epithelial cell proliferation
GO:0050707 regulation of cytokine secretion
GO:0050708 regulation of protein secretion
GO:0050709 negative regulation of protein secretion
GO:0050710 negative regulation of cytokine secretion
GO:0050714 positive regulation of protein secretion
GO:0050715 positive regulation of cytokine secretion
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050755 chemokine metabolic process
GO:0050764 regulation of phagocytosis
GO:0050766 positive regulation of phagocytosis
GO:0050777 negative regulation of immune response
GO:0050792 regulation of viral process
GO:0050796 regulation of insulin secretion
GO:0050810 regulation of steroid biosynthetic process
GO:0050830 defense response to Gram-positive bacterium
GO:0050900 leukocyte migration
GO:0050901 leukocyte tethering or rolling
GO:0050994 regulation of lipid catabolic process
GO:0050995 negative regulation of lipid catabolic process
GO:0051023 regulation of immunoglobulin secretion
GO:0051043 regulation of membrane protein ectodomain proteolysis
GO:0051044 positive regulation of membrane protein ectodomain proteolysis
GO:0051047 positive regulation of secretion
GO:0051048 negative regulation of secretion
GO:0051051 negative regulation of transport
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051147 regulation of muscle cell differentiation
GO:0051148 negative regulation of muscle cell differentiation
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051222 positive regulation of protein transport
GO:0051224 negative regulation of protein transport
GO:0051235 maintenance of location
GO:0051272 positive regulation of cellular component movement
GO:0051341 regulation of oxidoreductase activity
GO:0051346 negative regulation of hydrolase activity
GO:0051353 positive regulation of oxidoreductase activity
GO:0051384 response to glucocorticoid
GO:0051403 stress-activated MAPK cascade
GO:0051531 NFAT protein import into nucleus
GO:0051532 regulation of NFAT protein import into nucleus
GO:0051533 positive regulation of NFAT protein import into nucleus
GO:0051797 regulation of hair follicle development
GO:0051798 positive regulation of hair follicle development
GO:0051896 regulation of protein kinase B signaling
GO:0051897 positive regulation of protein kinase B signaling
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0055123 digestive system development
GO:0060425 lung morphogenesis
GO:0060441 epithelial tube branching involved in lung morphogenesis
GO:0060445 branching involved in salivary gland morphogenesis
GO:0060541 respiratory system development
GO:0060556 regulation of vitamin D biosynthetic process
GO:0060557 positive regulation of vitamin D biosynthetic process
GO:0060558 regulation of calcidiol 1-monooxygenase activity
GO:0060559 positive regulation of calcidiol 1-monooxygenase activity
GO:0060562 epithelial tube morphogenesis
GO:0060627 regulation of vesicle-mediated transport
GO:0060664 epithelial cell proliferation involved in salivary gland morphogenesis
GO:0060688 regulation of morphogenesis of a branching structure
GO:0060693 regulation of branching involved in salivary gland morphogenesis
GO:0060759 regulation of response to cytokine stimulus
GO:0061028 establishment of endothelial barrier
GO:0061046 regulation of branching involved in lung morphogenesis
GO:0061048 negative regulation of branching involved in lung morphogenesis
GO:0061138 morphogenesis of a branching epithelium
GO:0061756 leukocyte adhesion to vascular endothelial cell
GO:0061757 leukocyte adhesion to arterial endothelial cell
GO:0070265 necrotic cell death
GO:0070266 necroptotic process
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070304 positive regulation of stress-activated protein kinase signaling cascade
GO:0070371 ERK1 and ERK2 cascade
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070830 bicellular tight junction assembly
GO:0071216 cellular response to biotic stimulus
GO:0071219 cellular response to molecule of bacterial origin
GO:0071222 cellular response to lipopolysaccharide
GO:0071229 cellular response to acid chemical
GO:0071230 cellular response to amino acid stimulus
GO:0071312 cellular response to alkaloid
GO:0071316 cellular response to nicotine
GO:0071356 cellular response to tumor necrosis factor
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0071417 cellular response to organonitrogen compound
GO:0071450 cellular response to oxygen radical
GO:0071451 cellular response to superoxide
GO:0071550 death-inducing signaling complex assembly
GO:0071674 mononuclear cell migration
GO:0071675 regulation of mononuclear cell migration
GO:0071677 positive regulation of mononuclear cell migration
GO:0071800 podosome assembly
GO:0071801 regulation of podosome assembly
GO:0071803 positive regulation of podosome assembly
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0072564 blood microparticle formation
GO:0072567 chemokine (C-X-C motif) ligand 2 production
GO:0072593 reactive oxygen species metabolic process
GO:0072657 protein localization to membrane
GO:0072659 protein localization to plasma membrane
GO:0090002 establishment of protein localization to plasma membrane
GO:0090087 regulation of peptide transport
GO:0090150 establishment of protein localization to membrane
GO:0090153 regulation of sphingolipid biosynthetic process
GO:0090154 positive regulation of sphingolipid biosynthetic process
GO:0090276 regulation of peptide hormone secretion
GO:0090316 positive regulation of intracellular protein transport
GO:0090322 regulation of superoxide metabolic process
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097300 programmed necrotic cell death
GO:0097527 necroptotic signaling pathway
GO:0098542 defense response to other organism
GO:0098754 detoxification
GO:0098773 skin epidermis development
GO:0098869 cellular oxidant detoxification
GO:1900180 regulation of protein localization to nucleus
GO:1900182 positive regulation of protein localization to nucleus
GO:1900407 regulation of cellular response to oxidative stress
GO:1900409 positive regulation of cellular response to oxidative stress
GO:1901031 regulation of response to reactive oxygen species
GO:1901033 positive regulation of response to reactive oxygen species
GO:1901099 negative regulation of signal transduction in absence of ligand
GO:1901222 regulation of NIK/NF-kappaB signaling
GO:1901224 positive regulation of NIK/NF-kappaB signaling
GO:1901550 regulation of endothelial cell development
GO:1901615 organic hydroxy compound metabolic process
GO:1901617 organic hydroxy compound biosynthetic process
GO:1901668 regulation of superoxide dismutase activity
GO:1901671 positive regulation of superoxide dismutase activity
GO:1901888 regulation of cell junction assembly
GO:1901889 negative regulation of cell junction assembly
GO:1902105 regulation of leukocyte differentiation
GO:1902107 positive regulation of leukocyte differentiation
GO:1902115 regulation of organelle assembly
GO:1902117 positive regulation of organelle assembly
GO:1902593 single-organism nuclear import
GO:1902882 regulation of response to oxidative stress
GO:1902884 positive regulation of response to oxidative stress
GO:1902930 regulation of alcohol biosynthetic process
GO:1902932 positive regulation of alcohol biosynthetic process
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903140 regulation of establishment of endothelial barrier
GO:1903347 negative regulation of bicellular tight junction assembly
GO:1903409 reactive oxygen species biosynthetic process
GO:1903426 regulation of reactive oxygen species biosynthetic process
GO:1903428 positive regulation of reactive oxygen species biosynthetic process
GO:1903531 negative regulation of secretion by cell
GO:1903532 positive regulation of secretion by cell
GO:1903533 regulation of protein targeting
GO:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1903829 positive regulation of cellular protein localization
GO:1903900 regulation of viral life cycle
GO:1903901 negative regulation of viral life cycle
GO:1904407 positive regulation of nitric oxide metabolic process
GO:1904589 regulation of protein import
GO:1904591 positive regulation of protein import
GO:1904833 positive regulation of removal of superoxide radicals
GO:1904950 negative regulation of establishment of protein localization
GO:1904951 positive regulation of establishment of protein localization
GO:1904994 regulation of leukocyte adhesion to vascular endothelial cell
GO:1904996 positive regulation of leukocyte adhesion to vascular endothelial cell
GO:1904997 regulation of leukocyte adhesion to arterial endothelial cell
GO:1904999 positive regulation of leukocyte adhesion to arterial endothelial cell
GO:1905038 regulation of membrane lipid metabolic process
GO:1905330 regulation of morphogenesis of an epithelium
GO:1905331 negative regulation of morphogenesis of an epithelium
GO:1990748 cellular detoxification
GO:1990778 protein localization to cell periphery
GO:2000008 regulation of protein localization to cell surface
GO:2000010 positive regulation of protein localization to cell surface
GO:2000027 regulation of organ morphogenesis
GO:2000116 regulation of cysteine-type endopeptidase activity
GO:2000121 regulation of removal of superoxide radicals
GO:2000147 positive regulation of cell motility
GO:2000303 regulation of ceramide biosynthetic process
GO:2000304 positive regulation of ceramide biosynthetic process
GO:2000332 regulation of blood microparticle formation
GO:2000334 positive regulation of blood microparticle formation
GO:2000341 regulation of chemokine (C-X-C motif) ligand 2 production
GO:2000343 positive regulation of chemokine (C-X-C motif) ligand 2 production
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000379 positive regulation of reactive oxygen species metabolic process
GO:2000810 regulation of bicellular tight junction assembly
GO:2001056 positive regulation of cysteine-type endopeptidase activity
GO:2001057 reactive nitrogen species metabolic process
GO:2001233 regulation of apoptotic signaling pathway
GO:2001234 negative regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
GO:2001239 regulation of extrinsic apoptotic signaling pathway in absence of ligand
GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
Molecular Function GO:0002020 protease binding
GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
GO:0005164 tumor necrosis factor receptor binding
GO:0032813 tumor necrosis factor receptor superfamily binding
Cellular Component GO:0001891 phagocytic cup
GO:0009897 external side of plasma membrane
GO:0045121 membrane raft
GO:0055037 recycling endosome
GO:0098552 side of membrane
GO:0098589 membrane region
GO:0098857 membrane microdomain
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04060 Cytokine-cytokine receptor interaction
hsa04064 NF-kappa B signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04150 mTOR signaling pathway
hsa04210 Apoptosis
hsa04350 TGF-beta signaling pathway
hsa04380 Osteoclast differentiation
hsa04612 Antigen processing and presentation
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04640 Hematopoietic cell lineage
hsa04650 Natural killer cell mediated cytotoxicity
hsa04660 T cell receptor signaling pathway
hsa04664 Fc epsilon RI signaling pathway
hsa04668 TNF signaling pathway
hsa04920 Adipocytokine signaling pathway
Reactome R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-73887: Death Receptor Signalling
R-HSA-1266738: Developmental Biology
R-HSA-168256: Immune System
R-HSA-6783783: Interleukin-10 signaling
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-5357905: Regulation of TNFR1 signaling
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-75893: TNF signaling
R-HSA-5357956: TNFR1-induced NFkappaB signaling pathway
R-HSA-5357786: TNFR1-induced proapoptotic signaling
R-HSA-5626978: TNFR1-mediated ceramide production
R-HSA-5668541: TNFR2 non-canonical NF-kB pathway
R-HSA-381340: Transcriptional regulation of white adipocyte differentiation
Summary
SymbolTNF
Nametumor necrosis factor
Aliases TNFSF2; DIF; TNF-alpha; TNF superfamily, member 2; TNFA; tumor necrosis factor (TNF superfamily, member 2); ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TNF and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between TNF and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26896171MelanomaInhibit immunity (T cell function)In sharp contrast, DN-TNF treatment dramatically decreased IL1α and increased the essential immunoregulatory cytokines IL1β, IL12p70, and IL17 in the peripheral blood of MCA-injected mice. In addition, MDSC accumulation, STAT3 phosphorylation, and immunosuppression in MCA-injected mice were prevented by DN-TNF treatment, TNFR2-Fc treatment, and/or gene deletion of TNF or TNFR1, but not deletion of TNFR2.
26334519MelanomaPromote immunity (T cell function)In the tumor microenvironment, the combination therapy led to significantly downregulated levels of immunosuppressive factors, such as decreased numbers of myeloid-derived suppressor cells and regulatory T cells (Treg) cells and declined levels of interleukin-6 and chemokine ligand 2-in correlation with increased levels of proinflammatory cytokines, including tumor necrosis factor-α and IFN-γ as well as an elevation in the CD8(+) T-cell population.
26019274MelanomaPromote immunity (T cell function)Immunization in the presence of TPCS2a significantly increased activation of CD8 T cells compared with immunization without TPCS2a and as measured by CD8 T cell proliferation, production of proinflammatory IFN-γ, TNF-α, and IL-2, and prevention of tumor growth.
25977337MelanomaInhibit immunity (infiltration)Collectively, our observations indicate that TNF-R1-dependent TNF signaling impairs tumor-infiltrating CD8(+) T-cell accumulation and may serve as a putative target to favor CD8(+) T-cell-dependent immune response in melanoma.
27622331Colorectal CarcinomaPromote immunity (T cell function)These myeloid cells are phenotypically similar to inducible nitric oxide synthase (NOS2)- and tumor necrosis factor (TNF)-producing dendritic cells (DC), or Tip-DCs. Tumor elimination via NOS2 required the CD40-CD40L pathway. We also uncovered a strong correlation between survival of colorectal cancer patients and NOS2, CD40, and TNF expression in their tumors.
29273790MelanomaInhibit immunity (T cell function); immunotherapy targetTNFα blockade overcomes resistance to anti-PD-1 in experimental melanoma. Our recent work has highlighted that TNFR1-dependent TNF signalling impairs the accumulation of CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) in mouse melanoma. Herein, our results indicate that TNF or TNFR1 blockade synergizes with anti-PD-1 on anti-cancer immune responses towards solid cancers.
16488193Bronchogenic CarcinomaPromote immunity; increase the efficacy of immunotherapyBlockade of TNF-alpha decreases both inflammation and efficacy of intrapulmonary Ad.IFNbeta immunotherapy in an orthotopic model of bronchogenic lung cancer.
16397267Pancreatic carcinomaPromote immunity (T cell function)C57BL/6 EL-TGF-alpha x Trp53-/- mice, which develop spontaneous ductal pancreatic carcinoma, were generated. Intratumoral cytokine secretion of tumor necrosis factor-alpha, IFN-gamma, IL-6, and MCP-1 was lower in spontaneous tumors as well as the number of adoptively transferred tumor-specific T cells.
27407095Cervical carcinomaPromote immunityIntravaginal treatment of IL7-Fc, but not native IL7, induces upregulation of chemokines (CXCL10, CCL3, CCL4, and CCL5), cytokines (IFNγ, TNFα, IL6, and IL1β), and an adhesion molecule (VCAM-1) in the genital tract, leading to the recruitment of several leukocytes, including CD4, CD8, γδ T cells, and dendritic cells.
27357626MelanomaPromote immunityAntitumor efficacy was significantly enhanced with adenoviruses coding for murine interleukin-2 (mIL-2) and tumor necrosis factor-α (mTNFα) when compared with T-cell transfer alone or viruses alone. Mechanistic studies suggest that mIL-2 has an important role in activating T-cells at the tumor, while mTNFα induces chemokine expression.
28526770Ovarian CarcinomaPromote immunity (infiltration)We demonstrate superior antitumor efficacy for IgE compared with an otherwise identical IgG in a syngeneic immunocompetent animal, and we identify TNFα/MCP-1 signaling as an IgE-mediated mechanism of monocyte and macrophage activation and recruitment to tumors.
23389942Breast CarcinomaPromote immunityWe demonstrate that besides IFN-α, the production by Toll-like receptor (TLR)-activated healthy pDC of IFN-β and TNF-α but not IP-10/CXCL10 nor MIP1-α/CCL3 is impaired by the breast tumor environment. Indeed, recombinant TGF-β1 and TNF-α synergistically blocked IFN-α production of TLR-activated pDC, and neutralization of TGF-β and TNF-α in tumor-derived supernatants restored pDCs' IFN-α production.Importantly, we identified TGF-β and TNF-α as major soluble factors involved in TApDC functional alteration.
21278794Breast CarcinomaPromote immunitySecretion of pro-inflammatory cytokines by the senescent cells, particularly TNF-α and IFN-γ, mediates Fas upregulation. Indeed, treatment of proliferating cancer cell lines with TNF-α and IFN-γ, upregulates Fas expression, while blocking TNF-α and IFN-γ by using neutralizing antibodies, decreases Fas expression in senescent cells. We also demonstrate that NF-κB has a central role in controlling the senescence-associated secretory phenotype (SASP) by the premature senescent cells, and that TNF-α and IFN-γ, transcriptionally controlled by NF-κB, are the main mediators of Fas upregulation. Our data suggest the existence of an NF-κB-dependent autocrine loop, mediated by TNF-α and IFN-γ, responsible for expression of Fas on the surface of senescent cells, and for their killing.
21173239MelanomaPromote immunityClinical trials of CTLA-4-blocking antibodies to augment T-cell responses to malignant melanoma are at an advanced stage; however, little is known about the effects of CTLA-4 blockade on memory CD8(+) T-cell responses and the formation and maintenance of long-term CD8(+) T-cell memory. This is followed by an accumulation of memory cells that are capable of producing the effector cytokines IFN-γ and TNF-α.
19701890LeukemiaPromote immunityThe TNF member LIGHT also known as TL4 or TNFSF14) can play a major role in cancer control via its two receptors; it induces tumor cell death through lymphotoxin-beta receptor (LT-betaR) and ligation to the herpes virus entry mediator (HVEM) amplifies the immune response. By studying the effect of LIGHT in the transcriptional profile of a lymphoid malignancy, we found that HVEM, but not LT-betaR, stimulation induces a significant increase in the expression of chemokine genes such as IL-8, and an unexpected upregulation of apoptotic genes. This had functional consequences, since LIGHT, or HVEM mAb, thus far known to costimulate T- and B-cell activation, induced chronic lymphocytic leukemia cell death. Many of the mediators involved were identified here, with an apoptotic pathway as demonstrated by caspases activation, decrease in mitochondrial membrane potential, upregulation of the pro-apoptotic protein Bax, but also a role of TRAIL. HVEM Moreover, HVEM induced endogenous TNF-alpha production and TNF-alpha enhanced HVEM-mediated cell death.
29090321Hepatocellular CarcinomaInhibit immunity (T cell function)In the present study, we asked whether TNF-α can promote the expression of B7-H1 induced by IFN-γ in HCC cells. We found that JAK/STAT1/IRF1 was the primary pathway responsible for induction of B7-H1 expression by IFN-γ in human HCC cell lines. TNF-α and IFN-γ synergistically induced the expression of B7-H1 in the HCC cells. Moreover, the mechanism of the synergy was that TNF-α enhanced IFN-γ signaling by upregulating the expression of IFN-γ receptors.
16638868Fibrosarcoma; Colon CarcinomaPromote immunity (T cell function)Targeted delivery of tumor necrosis factor-alpha to tumor vessels induces a therapeutic T cell-mediated immune response that protects the host against syngeneic tumors of different histologic origin.
17925549Renal Cell CarcinomaInhibit immunityTumor necrosis factor alpha (TNF-alpha) may play a role in renal cell carcinoma (RCC). We performed two sequential phase II studies of infliximab, an anti-TNF-alpha monoclonal antibody, in patients with immunotherapy-resistant or refractory RCC. In study 1, three patients (16%) achieved partial response (PR) and three patients (16%) achieved stable disease (SD). Median duration of response (PR + SD) was 7.7 months (range, 5.0 to 40.5+ months). In study 2, 11 patients (61%) achieved SD. Median duration of response was 6.2 months (range, 3.5 to 24+ months).
24882582melanomaPromote immunity (T&NK cell function); essential for immunotherapytumor necrosis factor-α Cytokines, that is, interleukin-1β and tumor necrosis factor-α from MDSCs are required for B16 melanoma cell
29672044Colorectal CarcinomaPromote immunity (T&NK cell function); essential for immunotherapyWe found that andrographolide concentration-dependently inhibited TNF-α-induced IL-8 mRNA (2.23 ± 0.15 fold at 20 μM) and protein expression (4.78 ± 0.31 fold at 20 μM) and reduced the IL-8 transcriptional activity (2.59 ± 0.25 fold at 20 μM).
29668679breast carcinoma; ovarian carcinoma and glioblastomaPromote immunityAfter 2 days of co-culture, monocytes exposed to cancer cell lines showed markedly upregulated expression of M1-associated (TNF-α, IL-1β), M2-associated (CCL13, CD206), Mreg-associated (IL-10, TGF-β), and angiogenesis associated (MMP9, VEGF) genes.
29662549lung adenocarcinomaPromote immunity (infiltration)Increased cytokine values (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6 and IL-8) at the time of diagnosis and at 3 months after initiation of treatment were significantly correlated with improved response to immunotherapy and prolonged OS.
29603739glioblastomaPromote immunity (infiltration)By using the peptide CGKRK to deliver the tumour necrosis factor (TNF) superfamily member LIGHT (also known as TNF superfamily member 14; TNFSF14) to angiogenic tumour vessels, we have generated a reagent that normalizes the brain cancer vasculature by inducing pericyte contractility and re-establishing endothelial barrier integrity.
29573850all types of cancerPromote immunityTen patients required additional immunosuppression beyond corticosteroids, with TNF-inhibitors and/or methotrexate.
21540234Renal Cell CarcinomaPromote immunityWe found that the combination treatment also increased macrophage production of TNFα, which played an indispensable role in activation of the observed antitumor immune response.
29327244MyelomaPromote immunityAntibody-based delivery of tumor necrosis factor (L19-TNFα) and interleukin-2 (L19-IL2) to tumor-associated blood vessels has potent immunological and anticancer activity in the syngeneic J558L BALB/c myeloma model. IL2, TNFα, or IL2 plus TNFα (final 20 h) increased the proportion of CD4- CD25low effector lymphocytes possibly indicating immune activation.
15940614Colorectal CancinomaInhibit immunity (T cell function)These data show that colorectal cancer induces T-cell apoptosis through the release of Fas ligand-bearing and tumor necrosis factor-related apoptosis-inducing ligand-bearing microvesicles both in vitro and in vivo.
29490991Prostate Carcinoma; MelanomaPromote immunity (infiltration); Essential for immunotherapyTargeting the tumor vasculature with low-dose TNF in association with ACT may represent a novel strategy for enhancing T-cell infiltration in tumors and overcoming resistance to immune checkpoint blockers. NGR The combination of ACT, NGR-TNF and ICB was the most effective in delaying disease progression, and in improving overall survival of mice bearing ICB-resistant prostate cancer or melanoma.
24446520MelanomaPromote immunityTNF-α-dependent hematopoiesis following Bcl11b deletion in T cells restricts metastatic melanoma. Moreover, TNF-α treatment of wild-type mice also reduced the tumor burden and increased hematopoiesis and the numbers and activity of NK cells in the lung. In vitro treatment with TNF-α of lineage-negative hematopoietic progenitors increased NK and myeloid differentiation, further supporting a role of TNF-α in promoting hematopoiesis.
24379122Breast CarcinomaInhibit immunityIndeed, we found that tmTNF-α, rather than secretory TNF-α (sTNF-α), activated MDSCs with enhanced suppressive activities, including upregulating arginase-1 and inducible NO synthase transcription, promoting secretion of NO, reactive oxygen species, IL-10, and TGF-β, and enhancing inhibition of lymphocyte proliferation.
24081947Lung CarcinomaInhibit immunityTNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects.
21670304PapillomaPromote immunityResistance to papilloma development in Tnf(-/-) mice was associated with increased IFN-γ and CD8(+) T cells in skin and a significant reduction in IL-10-producing B regulatory cells alongside an increase in IFN-γ-producing CD8(+) T cells in the spleen.
20613784Chronic Lymphocytic LeukemiaInhibit immunity; Immunotherapy targetB-cell chronic lymphocytic leukemia (CLL) is characterized by slow accumulation of malignant cells, which are supported in the microenvironment by cell-cell interactions and soluble cytokines such as tumor necrosis factor (TNF). We evaluated the effect of the small molecule TNF inhibitor LMP-420 on primary CLL cells. These changes were associated with decreased expression of anti-apoptotic proteins Mcl-1, Bcl-xL and Bcl-2. In addition, LMP-420 potentiated the cytotoxic effect of fludarabine and inhibited in vitro proliferation of stimulated CLL cells. Gene expression profiling indicated that the mechanism of action of LMP-420 may involve suppression of nuclear factor-kappaB and immune response pathways in CLL cells.
20308315GliomaPromote immunityIn vitro, pDC produced more TNF-alpha than uDC: addition of TNF-alpha to the medium decreased the proliferation of glioma cells. Overall, the results suggest that IT-pDC potentiates the anti-tumor immune response elicited by SC-pDC by pro-immune modulation of cytokines in the tumor microenvironment, decrease of Treg cells, and direct inhibition of tumor proliferation by TNF-alpha.
29887396Colorectal NeoplasmPromote immunity; Essential for immunotherapyWe further demonstrate that T cell-derived tumor necrosis factor alpha (TNF-α) can synergize with chemotherapy to intensify oxidative stress and tumor cell death in an NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase-dependent manner. Reduction of oxidative stress, by preventing TNF-α-signaling in tumor cells or scavenging ROS, antagonized the therapeutic effects of adoptive immunotherapy.
29721376Non-Small Cell Lung CarcinomaInhibit immunityWe also demonstrated that the expression of PD-L1 required both TNFα and TGFβ1. Indeed, TGFβ1 decreased DNMT1 content and that resulted in PD-L1 promoter demethylation whereas TNFα induced the NF-κB pathway that promoted expression of demethylated PD-L1 promoter.
29721366MelanomaPromote immunity; Essential for immunotherapyTNFa and IL-2 armed adenoviruses enable complete responses by anti-PD-1 checkpoint blockade. Viral expression of IL2 and TNFa altered the cytokine balance in the tumor microenvironment towards Th1 and increased the intratumoral proportion of CD8+ and conventional CD4+ T cells.
17475896Renal Cell CarcinomaInhibit immunityTNF-alpha induction of GM2 expression on renal cell carcinomas promotes T cell dysfunction. In this study, we report that TNF-alpha secreted by infiltrating inflammatory cells and/or genetically modified tumors augments tumor-associated GM2 levels, which leads to T cell death and immune dysfunction. TNF-alpha increases GM2 ganglioside expression by enhancing the mRNA levels encoding its synthetic enzyme, GM2 synthase, as demonstrated by both RT-PCR and Southern analysis.
25225903colorectal carcinomaPromote immunityWe have demonstrated a significant positive correlation between the expression of TNF and IFNG, reiterating the fact that both these cytokines act through TH1 pathways that are associated with immune deviation towards enhanced or suppressed tumour rejection based on their activity
25209187colorectal carcinomaInhibit immunityCPT11 also directly affects MDSCs by boosting secretion of proinflammatory cytokines such as TNFa, which is a key MDSC regulator, inducing their differentiation arrest via S100A8/9 and increasing their suppressive activity
25205103lymphomaPromote immunityRecombinant HMGN1 induced the accumulation and activation of DCs at the site of injection as indicated by upregulation of costimulatory and MHC molecules as well as extracellular secretion of proinflammatory cytokines such as TNFa, IL12 p70, and IL1b
25125657melanomaPromote immunity(T cell function)Here, we show that CCDC134 is differentially expressed on resting and activated immune cells and that it promotes CD8(+) T-cell activation, proliferation, and cytotoxicity by augmenting expression of the T-cell effector molecules IFNγ, TNFα, granzyme B, and perforin
23225218Hepatocellular CarcinomaPromote immunityHowever, in patients with advanced-stage HCC, NK cells were significantly decreased in number with impaired tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) production.Further kinetic experiments revealed that soon after exposure to tumor-derived monocytes, NK cells underwent a rapid, transient activation, but then they became exhausted, and eventually died.
21852386Breast CarcinomaInhibit immunityTaken together, our results show a dialogue between NK and tumor cells leading to IFN-γ secretion, which in turn associates with monocyte-derived IL-1β and TNF-α to drive production of CCL22 by tumor cells and subsequent recruitment of T(reg) to evade this early antitumor immune response.
21796616MelanomaPromote immunityThe production of multiple cytokines (IFNgamma, TNFalpha, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells. Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways.
16990769leukemiaPromote immunityAfter 21-day co-culture with DC pulsed with CD40L+ apoptotic BCP-ALL blasts, T cells presented with both effector and central memory phenotype, and showed high and specific cytotoxic activity against leukemic cells (average lysis = 77%), mostly mediated by CD8+ T cells. Noticeably, growth of CD4 T cells was maintained (45% of total cells), which actively produced Th1 cytokines (IFN-gamma, TNF-alpha, IL-2), but not IL-4, IL-5 and IL-10.
16982774MelanomaInhibit immunityCD14+ monocytes isolated from healthy donors and differentiated with interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor in the presence of tumor-derived microvesicles turned into HLA-DR(-/low) cells, retaining CD14 expression and failing to up-regulate costimulatory molecules, such as CD80 and CD86.These phenotypic changes were paralleled by a significant release of different cytokines, including IL-6, tumor necrosis factor-alpha, and transforming growth factor-beta (TGF-beta), and a dose-dependent suppressive activity on activated T-cell-proliferation and cytolytic functions, which could be reversed by anti-TGF-beta-neutralizing antibodies.
11875499colon carcinomaPromote immunityCTL and NK cells promote tumor cell apoptosis with delivery of perforin and granzymes directly into cells or through the extrinsic pathway, inducing apoptotic death by triggering death receptors by the TNF family of molecules, including TRAIL, TNF- , Fas ligand (FasL), and lymphotoxin (LT), thereby inducing apoptosis in cells.
Summary
SymbolTNF
Nametumor necrosis factor
Aliases TNFSF2; DIF; TNF-alpha; TNF superfamily, member 2; TNFA; tumor necrosis factor (TNF superfamily, member 2); ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of TNF in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolTNF
Nametumor necrosis factor
Aliases TNFSF2; DIF; TNF-alpha; TNF superfamily, member 2; TNFA; tumor necrosis factor (TNF superfamily, member 2); ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of TNF in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)141201
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)6501
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)8701
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.5940.334
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-1.0170.317
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.0430.977
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.5120.4
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.0560.248
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0480.96
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.1730.133
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.8280.0794
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2470.235
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TNF in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolTNF
Nametumor necrosis factor
Aliases TNFSF2; DIF; TNF-alpha; TNF superfamily, member 2; TNFA; tumor necrosis factor (TNF superfamily, member 2); ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TNF. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolTNF
Nametumor necrosis factor
Aliases TNFSF2; DIF; TNF-alpha; TNF superfamily, member 2; TNFA; tumor necrosis factor (TNF superfamily, member 2); ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TNF. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TNF.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTNF
Nametumor necrosis factor
Aliases TNFSF2; DIF; TNF-alpha; TNF superfamily, member 2; TNFA; tumor necrosis factor (TNF superfamily, member 2); ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TNF. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTNF
Nametumor necrosis factor
Aliases TNFSF2; DIF; TNF-alpha; TNF superfamily, member 2; TNFA; tumor necrosis factor (TNF superfamily, member 2); ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TNF expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTNF
Nametumor necrosis factor
Aliases TNFSF2; DIF; TNF-alpha; TNF superfamily, member 2; TNFA; tumor necrosis factor (TNF superfamily, member 2); ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TNF and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTNF
Nametumor necrosis factor
Aliases TNFSF2; DIF; TNF-alpha; TNF superfamily, member 2; TNFA; tumor necrosis factor (TNF superfamily, member 2); ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TNF collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting TNF.
ID Name Drug Type Targets #Targets
DB00005EtanerceptBiotechC1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......14
DB00051AdalimumabBiotechC1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......12
DB00065InfliximabBiotechTNF1
DB00608ChloroquineSmall MoleculeGSTA2, TLR9, TNF3
DB00668EpinephrineSmall MoleculeADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, ADRB ......12
DB00852PseudoephedrineSmall MoleculeADRA1A, ADRA2A, ADRB1, ADRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, ......20
DB01041ThalidomideSmall MoleculeCRBN, FGFR2, NFKB1, ORM1, ORM2, PTGS2, TNF7
DB01296GlucosamineSmall MoleculeIFNG, MMP9, NFKB2, TNF4
DB01407ClenbuterolSmall MoleculeADRB1, ADRB2, ADRB3, NGF, TNF5
DB01411PranlukastSmall MoleculeCYSLTR1, IL5, MUC2, NFKB1, RNASE3, TNF6
DB01427AmrinoneSmall MoleculePDE3A, PDE4B, TNF3
DB02325Isopropyl AlcoholSmall MoleculeACP5, ADI1, AHCY, CHIT1, DCXR, DDX39B, GCH1, GDF5, GM2A, PLA2G2A, ......15
DB04956AfelimomabBiotechTNF1
DB05017YSIL6Small MoleculeIL6, TNF2
DB05207SD118Small MoleculeIL1R1, TNF2
DB05218PN0621BiotechTNF1
DB05303OMS-103HPSmall MoleculeIL1R1, TNF2
DB05412TalmapimodSmall MoleculeIL1B, MAPK14, MT-CO2, TNF4
DB05470VX-702Small MoleculeIL1B, IL6, MAPK14, TNF4
DB05513AtiprimodSmall MoleculeIL6, TNF2
DB05676ApremilastSmall MoleculeIFNG, IL2, NOS3, PDE4A, PDE4B, PDE4D, TNF7
DB05744CRx-139Small MoleculeCRP, IL10, IL6, TNF4
DB05758CYT007-TNFQbBiotechTNF1
DB05767AndrographolideSmall MoleculeIL1B, IL6, NFKB1, NFKB2, TNF5
DB05869Ethyl pyruvateSmall MoleculeHMGB1, TNF2
DB05879AME-527BiotechTNF1
DB05968PR-104Small MoleculeTNF1
DB05992PlinabulinSmall MoleculeTNF1
DB06444DexanabinolSmall MoleculeTNF1
DB06495OnerceptBiotechTNF1
DB06674GolimumabBiotechTNF1
DB08904Certolizumab pegolBiotechTNF1
DB08910PomalidomideSmall MoleculeCRBN, PTGS2, TNF3
DB09221PolaprezincSmall MoleculeFLT1, HSP90AA1, HSP90AB1, IL3, IL6, NGF, PDGFRB, TNF8
DB11967BinimetinibSmall MoleculeIL1B, IL6, TNF3
DB12140DilmapimodSmall MoleculeIL1B, IL6, TNF3