Immune Checkpoint Signaling Pathway Download...Tumor-draining Lymph Node NK T-bet Th2 Proliferation...
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Cell Signaling Technology © 2003–2018 Cell Signaling Technology, Inc. www.cellsignal.com Direct Stimulatory Modification Direct Inhibitory Modification Multistep Stimulatory Modification Multistep Inhibitory Modification Tentative Stimulatory Modification Tentative Inhibitory Modification Transcriptional Inhibitory Modification Pathway Diagram Key Immune Checkpoint Signaling in the TME Galectin-9 B7-1/B7-2 B7-H3 B7-H4 PD-L1/ PD-L2 B7-H3 ? 4-1BBL B7-1/B7-2 GITRL ICOSL OX40L CD40 MHC TIM-3 VISTA ? ? ? LAG-3 CTLA-4 PD-1 OX40 (CD143) 4-1BB CD28 GITR ICOS CD40L TCR VISTA ? Tumor- specific CD4 + T cell B cell DC Dendritic Cell Tumor-promoting Macrophage M2 Macrophage M1 Macrophage Mast cell Tumor-specific T cell Cytotoxic granules IFNγ-R IFNγ TGF-β IFNγ MMPs TGF-β IL-1β TNF-α IL-1β TNF-α IL-6R ALK ROS1 EGFR HER2 etc. IL-4 IL-13 IL-6 Oncogenic signaling IL-10 MMPs CCL22 TNF-R CTL T Reg FoxP3 + CD4 + IL-10 TGF-β IL-35 IL-10 TGF-β IL-1β TNF-α TNF-α IL-2 Cytotoxic granules Arginase T-bet MMPs VEGF IL-10 IDO CCL22 T-bet Th1 MSC T cell priming Naive T cell Angiogenesis MMPs VEGF Tumor-draining Lymph Node NK T-bet Th2 Proliferation and production of anti-tumor antibodies IL-2, 4, 5 Activation/Response Change Inflammation Class I antigen presentation; IDO; PD-L1 and other co-inhibitory receptors Genes of cell growth and survival; PD-L1 and other co-inhibitory receptors Nucleus Tumor Cell NF-κB Stat1 Stat3 Stat3 Akt Jak MAPK RTK Jak T cell apoptosis Arginase Arginase Co-inhibitory receptor-ligand complex Co-stimulatory receptor-ligand complex
Transcript of Immune Checkpoint Signaling Pathway Download...Tumor-draining Lymph Node NK T-bet Th2 Proliferation...
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Cell Signaling Technology
© 2003–2018 Cell Signaling Technology, Inc.
www.cellsignal.com
Direct Stimulatory Modification
Direct Inhibitory Modification
Multistep Stimulatory Modification
Multistep Inhibitory Modification
Tentative Stimulatory Modification
Tentative Inhibitory Modification
Transcriptional Inhibitory Modification
Pathway Diagram Key
Immune Checkpoint Signaling in the TME
Phospholipid Signaling PW
Gal
ectin
-9
B7-
1/B
7-2
B7-
H3
B7-
H4
PD
-L1/
PD
-L2
B7-
H3
?
4-1B
BL
B7-
1/B
7-2
GIT
RL
ICO
SL
OX
40L
CD
40
MH
C
TIM
-3
VIS
TA? ?? LA
G-3
CTL
A-4
PD
-1
OX
40(C
D14
3)
4-1B
BC
D28
GIT
R
ICO
S
CD
40L
TCR
VIS
TA ?
Tumor-specific
CD4+T cellB cellDC
Dendritic Cell
Tumor-promoting Macrophage
M2Macrophage
M1Macrophage
Mast cell
Tumor-specificT cell
Cytotoxicgranules
IFNγ-R
IFNγ
TGF-β
IFNγ
MMPsTGF-β
IL-1βTNF-α
IL-1βTNF-α
IL-6R
ALKROS1EGFRHER2etc.
IL-4
IL-13
IL-6
Oncogenicsignaling
IL-10
MMPs
CCL22
TNF-R
CTL
TReg
FoxP3+
CD4+
IL-10TGF-β
IL-35
IL-10TGF-β
IL-1βTNF-α
TNF-αIL-2
Cytotoxic granules
Arginase
T-bet
MMPsVEGF
IL-10IDO
CCL22
T-betTh1
MSC
T cellpriming
NaiveT cell
Angiogenesis
MMPsVEGF
Tumor-draining Lymph Node
NKT-bet
Th2
Proliferation and production of anti-tumor antibodies
IL-2, 4, 5
Activation/Response Change
Inflammation
Class I antigen presentation;IDO; PD-L1 and other co-inhibitory receptors
Genes of cell growth and survival;PD-L1 and other co-inhibitory receptors
Nucleus
Tumor Cell
NF-κB
Stat1
Stat3
Stat3
Akt
Jak
MAPK
RTKJak
T cell apoptosis
Arginase
Arginase
Co-inhibitory receptor-ligand complex
Co-stimulatory receptor-ligand complex
