Immune Checkpoint Signaling in the Tumor Microenvironment · in the Tumor Microenvironment...
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www.cellsignal.com/checkpoints For pathway key and background please visit: Immune Checkpoint Signaling in the Tumor Microenvironment 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 in the Tumor Microenvironment · in the Tumor Microenvironment...
www.cellsignal.com/checkpointsFor pathway key and background please visit:
Immune Checkpoint Signaling in the Tumor Microenvironment
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
www.cellsignal.com/cellbiologyFor Research Use Only. Not For Use In Diagnostic Procedures.
17-I
MM
-259
-FLY
1-E1
www.cellsignal.com/cellbiologyFor pathway key and background please visit:
APPLICATIONS & REACTIVITY KEY: WB Western Blotting / IP Immunoprecipitation / IHC Immunohistochemistry / IF Immunofluorescence / F Flow Cytometry / ChIP Chromatin Immunoprecipitation / -IC Immunocytochemistry / -P Paraffin / -F Frozen / E-P Peptide ELISA / H human / M mouse / R rat / Hm hamster / Mk monkey / C chicken / Mi mink / Dm D. melanogaster / X Xenopus / Z zebra fish / B bovine / Dg dog / Pg pig / Sc S. cerevisiae / All all species expected / ( ) 100% sequence homology
For pathway key and background please visit:
For Research Use Only. Not For Use In Diagnostic Procedures.
www.cellsignal.com/checkpoints
© 2018 Cell Signaling Technology, Inc. Cell Signaling Technology, and CST are trademarks of Cell Signaling Technology, Inc. U.S. Patent No. 5,675,063. All other trademarks are the property of their respective owners.
Key Products for Immune Checkpoint Signaling in the TMEVisit www.cellsignal.com for full listing of antibodies, related kits, and reagents.
CD8α (D4W2Z) XP® Rabbit mAb (Mouse Specific) #98941: IHC analysis of paraffin-embedded mouse spleen using #98941.
PD-1 (D4W2J) XP® Rabbit mAb #86163: IHC analysis of paraffin-embedded human B-cell non-Hodgkin’s lymphoma using #86163.
PD-L1 (E1L3N®) XP® Rabbit mAb #13684: IHC analysis of paraffin-embedded human lung carcinoma using #13684.
PD-L2 (D7U8C™) XP® Rabbit mAb #82723: IHC analysis of paraffin-embedded human non-small cell lung carcinoma using #82723.
TIM-3 (D5D5R™) XP® Rabbit mAb #45208: IHC analysis of paraffin-embedded human colon carcinoma using #45208.
ANTIBODIES & KITS APPLICATIONS REACTIVITY
#34594 4-1BB/CD137/TNFRSF9 (D2Z4Y) Rabbit mAb WB, IP, IHC-P, IF-IC, F H
#62634 4-1BB/CD137/TNFRSF9 Antibody WB H
#93668 Arginase-1 (D4E3M™) XP® Rabbit mAb WB, IHC-P, IF-IC, IF-F, F H, M, R
#14058 B7-H3 (D9M2L) XP® Rabbit mAb WB, IHC-P H
#14572 B7-H4 (D1M8I) XP® Rabbit mAb WB, IHC-P H
#14520 PathScan® Total B7-H4 Sandwich ELISA Kit ELISA H
#45581 CD11c (D3V1E) XP® Rabbit mAb WB, IHC-P H
#38774 CD28 (D2Z4E) Rabbit mAb WB, IP H, M
#4443 CD3ε (CD3-12) Rat mAb WB, IP F H, M (Pg)
#85061 CD3ε (D7A6E™) XP® Rabbit mAb WB, IP IHC-P H
#25229 CD4 (D7D2Z) Rabbit mAb WB, IHC-P M, R
#40868 CD40 (D8W3N) Rabbit mAb WB, IHC-P H
#15094 CD40 Ligand (D5J9Y) Rabbit mAb WB, IP, IHC-P H
#76437 CD68 (D4B9C) XP® Rabbit mAb IHC-P, IF-IC, F H
#79594 CD68 (D4B9C) XP® Rabbit mAb (PE Conjugate) F H
#70306 CD8α (C8/144B) Mouse mAb (IHC Specific) IHC-P H
#98941 CD8α (D4W2Z) XP® Rabbit mAb (Mouse Specific) WB, IHC-P M
#85336 CD8α (D8A8Y) Rabbit mAb WB, IP, IHC-P, F H
#15162 CTLA-4 (D4E9I) Rabbit mAb (Alexa Fluor® 488 Conjugate)
F H
#15132 CTLA-4 (D4E9I) Rabbit mAb (PE Conjugate) F H
#70076 F4/80 (D2S9R) XP® Rabbit mAb WB, IP, IHC-P M
#98377 FoxP3 (D2W8E™) Rabbit mAb (IHC Specific) IHC-P H
#12653 FoxP3 (D6O8R) Rabbit mAb IHC-P, IF-F, F M
#40103 Galectin-1/LGALS1 (8A12) Mouse mAb WB, IHC-P H
#12936 Galectin-1/LGALS1 (D608T) Rabbit mAb WB, IF-IC H, M, R, Mk
#13888 Galectin-1/LGALS1 (D608T) Rabbit mAb (IHC Formulated)
IHC-P H, M, R
#54330 Galectin-9 (D9R4A) XP® Rabbit mAb WB, IHC-P F H
#68014 GITR (D9I9D) Rabbit mAb (IHC Preferred) WB, IHC-P H, (Mk)
#4928 Granzyme A Antibody WB, E-P H
#4275 Granzyme B Antibody WB, E-P H, M
#89601 ICOS (D1K2T™) Rabbit mAb (IHC Specific) IHC-P H
#86630 IDO (D5J4E™) Rabbit mAb WB, IP, IHC-P, IF-IC, F H
#10312 IDO (D5J4E™) Rabbit mAb (PE Conjugate) F H
#15372 LAG3 (D2G4O™) XP® Rabbit mAb WB, IHC-P H
#13160 NT5E/CD73 (D7F9A) Rabbit mAb WB, IHC-P H, M, R
#15123 OX40 (D1S6L) Rabbit mAb WB, IP, IF-IC, F H
#15135 OX40 (D1S6L) Rabbit mAb (Alexa Fluor® 488 Conjugate)
IF-IC, F H
ANTIBODIES & KITS APPLICATIONS REACTIVITY
#59036 OX40L (D6K7R) Rabbit mAb (IHC Specific) IHC-P H
#15135 OX40 (D1S6L) Rabbit mAb (Alexa Fluor® 488 Conjugate)
IF-IC, F H
#59036 OX40L (D6K7R) Rabbit mAb (IHC Specific) IHC-P H
#13160 NT5E/CD73 (D7F9A) Rabbit mAb WB, IHC-P H, M, R
#15123 OX40 (D1S6L) Rabbit mAb WB, IP, IF-IC, F H
#15135 OX40 (D1S6L) Rabbit mAb (Alexa Fluor® 488 Conjugate)
IF-IC, F H
#59036 OX40L (D6K7R) Rabbit mAb (IHC Specific) IHC-P H
#86163 PD-1 (D4W2J) XP® Rabbit mAb WB, IP, IHC-P, F H
#84651 PD-1 (D7D5W) XP® Rabbit mAb (Mouse Specific) WB, IHC-P, F H, Mk
#29122 PD-L1 (405.9A11) Mouse mAb WB, IHC-P H
#64988 PD-L1 (D5V3B) Rabbit mAb (Mouse Specific; IHC Specific)
IHC-P M
#14123 PD-L1 (E1L3N®) XP® Rabbit mAb (PE Conjugate) F H
#13684 PD-L1 (E1L3N® ) XP® Rabbit mAb WB, IP, IHC-P, F H
#14772 PD-L1 (E1L3N®) XP® Rabbit mAb (Alexa Fluor® 488 Conjugate)
F H
#15005 PD-L1 (E1L3N®) XP® Rabbit mAb (Alexa Fluor® 647 Conjugate)
F H
#86744 PD-L1 (Extracellular Domain Specific) (D8T4X) Rabbit mAb
IF-IC, F H
#25048 PD-L1 (Extracellular Domain Specific) (D8T4X) Rabbit mAb (Alexa Fluor® 488 Conjugate)
IF-IC, F H
#41726 PD-L1 (Extracellular Domain Specific) (D8T4X) Rabbit mAb (Alexa Fluor® 647 Conjugate)
IF-IC, F H
#55919 PD-L1 (Extracellular Domain Specific) (D8T4X) Rabbit mAb (Pacific Blue™ Conjugate)
F H
#71391 PD-L1 (Extracellular Domain Specific) (D8T4X) Rabbit mAb (PE Conjugate)
F H
#15165 PD-L1 (Extracellular Domain Specific) (E1J2J™) Rabbit mAb
WB, IHC-P H
#14784 PathScan® Total PD-L1 Sandwich ELISA Kit ELISA H
#82723 PD-L2 (D7U8C™) XP® Rabbit mAb WB, IHC-P H
#81254 PVR/CD155 (D8A5G) Rabbit mAb WB, IHC-P H
#83882 TIM-3 (D3M9R) XP® Rabbit mAb (Mouse Specific) WB, IP, IHC-P M
#45208 TIM-3 (D5D5R™) XP® Rabbit mAb WB, IP, IHC-P, F H
#54669 TIM-3 (D5D5R™) XP® Rabbit mAb (Alexa Fluor® 488 Conjugate)
F H
#78226 TIM-3 (D5D5R™) XP® Rabbit mAb (Alexa Fluor® 647 Conjugate)
F H
#64953 VISTA (D1L2G™) XP® Rabbit mAb WB, IHC-P, F H, Mk
#54979 VISTA (D5L5T) XP® Rabbit mAb WB, IP, IHC-P, IF H, M, R
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