CellSignalingTechnology©2003–2018CellSignalingTechnology,Inc.www.cellsignal.comDirectStimulatoryModificationDirectInhibitoryModificationMultistepStimulatoryModificationMultistepInhibitoryModificationTentativeStimulatoryModificationTentativeInhibitoryModificationTranscriptionalInhibitoryModificationPathwayDiagramKeyImmuneCheckpointSignalingintheTMEPhospholipidSignalingPWGalectin-9B7-1/B7-2B7-H3B7-H4PD-L1/PD-L2B7-H3?4-1BBLB7-1/B7-2GITRLICOSLOX40LCD40MHCTIM-3VISTA???LAG-3CTLA-4PD-1OX40(CD143)4-1BBCD28GITRICOSCD40LTCRVISTA?Tumor-specificCD4+TcellBcellDCDendriticCellTumor-promotingMacrophageM2MacrophageM1MacrophageMastcellTumor-specificTcellCytotoxicgranulesIFNγ-RIFNγTGF-βIFNγMMPsTGF-βIL-1βTNF-αIL-1βTNF-αIL-6RALKROS1EGFRHER2etc.IL-4IL-13IL-6OncogenicsignalingIL-10MMPsCCL22TNF-RCTLTRegFoxP3+CD4+IL-10TGF-βIL-35IL-10TGF-βIL-1βTNF-αTNF-αIL-2CytotoxicgranulesArginaseT-betMMPsVEGFIL-10IDOCCL22T-betTh1MSCTcellprimingNaiveTcellAngiogenesisMMPsVEGFTumor-drainingLymphNodeNKT-betTh2Proliferationandproductionofanti-tumorantibodiesIL-2,4,5Activation/ResponseChangeInflammationClassIantigenpresentation;IDO;PD-L1andotherco-inhibitoryreceptorsGenesofcellgrowthandsurvival;PD-L1andotherco-inhibitoryreceptorsNucleusTumorCellNF-κBStat1Stat3Stat3AktJakMAPKRTKJakTcellapoptosisArginaseArginaseCo-inhibitoryreceptor-ligandcomplexCo-stimulatoryreceptor-ligandcomplex
