TY - JOUR T1 - Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-017-0257-y VL - 5 IS - 1 SP - 53 AU - Michael A. Cannarile AU - Martin Weisser AU - Wolfgang Jacob AU - Anna-Maria Jegg AU - Carola H. Ries AU - Dominik Rüttinger Y1 - 2017/12/01 UR - http://jitc.bmj.com/content/5/1/53.abstract N2 - The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. Emerging data on the tolerability of CSF1/CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents. The specificity of these agents and their potent blocking activity has been substantiated by impressive response rates in diffuse-type tenosynovial giant cell tumors, a benign connective tissue disorder driven by CSF1 in an autocrine fashion. In the malignant disease setting, data on the clinical activity of immunotherapy combinations with CSF1/CSF1R-targeting agents are pending. As our knowledge of macrophage biology expands, it becomes apparent that the complex phenotypic and functional properties of macrophages are heavily influenced by a continuum of survival, differentiation, recruitment, and polarization signals within their specific tissue environment. Thus, the role of macrophages in regulating tumorigenesis and the impact of depleting and/or reprogramming TAM as therapeutic approaches for cancer patients may vary greatly depending on organ-specific characteristics of these cells. We review the currently available clinical safety and efficacy data with CSF1/CSF1R-targeting agents and provide a comprehensive overview of ongoing clinical studies. Furthermore, we discuss the local tissue macrophage and tumor-type specificities and their potential impact on CSF1/CSF1R-targeting treatment strategies for the future.Abbreviations:AEAdverse eventALTAlanine aminotransferaseASTAspartate aminotransferaseATCAnaplastic thyroid cancerBPIBrief Pain InventoryCBRClinical benefit ratecHLClassical Hodgkin lymphomaCNSCentral nervous systemCRCColorectal cancerCSF1Colony-stimulating factor 1CSF1RColony-stimulating factor 1 receptorCTLA4Cytotoxic T-lymphocyte-associated protein 4DCDendritic cellsDLTDose-limiting toxicitydt-GCTDiffuse-type tenosynovial giant cell tumorsEMTEpithelial to mesenchymal transitionFLT3fms-like tyrosine kinase 3GBMGlioblastomaGCT-TSGiant cell tumor of the tendon sheathGISTGastrointestinal stromal tumorGM-CSFGranulocyte-macrophage colony-stimulating factorHLA-DRHuman leukocyte antigen-antigen D relatedIDOIndolamin-2,3-DioxygenaseIFNγInterferon γIGF-1Insulin-like growth factor 1IHCImmunohistochemistryILInterleukiniNOSInducible nitric oxide synthasemAbMonoclonal antibodyMCSFMacrophage colony-stimulating factorMDSCMyeloid derived suppressor cellsMECMucoepidermoid carcinoma of the lungMPNSTMalignant peripheral nerve sheath tumorMSIMicrosatellite instabilityMSSMicrosatellite stableMTDMaximum tolerated doseNRSNumeric rating scaleNSCLCNon-small cell lung cancerORRObjective response ratePD1Programmed cell death protein 1PDGFRPlatelet-derived growth factor receptorPDL1Programmed cell death-ligand 1PFSProgression-free survivalPPAR-γPeroxisome proliferator-activated receptor-γPROMISPatient-Reported Outcomes Measurement Information SystemPVNSPigmented villonodular synovitisRCCRenal cell carcinomaSCCHNSquamous cell carcinoma of the head and neckTAMTumor-associated macrophagesTh cellsT helper cellsTMETumor microenvironmentTNBCTriple-negative breast cancerTNFαTumor necrosis factor αTRAILTumor necrosis factor related apoptosis inducing ligandUBCUrothelial bladder carcinomaVEGFVascular Endothelial Growth FactorWOMACWestern Ontario and McMasters Universities Osteoarthritis Index ER -