CancerCellPerspectiveTheMicroenvironmentalLandscapeofBrainTumorsDanielaF.Quail1,2andJohannaA.Joyce3,4,*1GoodmanCancerResearchCentre2DepartmentofPhysiologyMcGillUniversity,Montreal,QCH3A1A3,Canada3LudwigInstituteforCancerResearch,UniversityofLausanne,1066Lausanne,Switzerland4DepartmentofOncology,UniversityofLausanne,ChemindesBoveresses155,1066Lausanne,Switzerland*Correspondence:johanna@joycelab.orghttp://dx.doi.org/10.1016/j.ccell.2017.02.009Thebraintumormicroenvironment(TME)isemergingasacriticalregulatorofcancerprogressioninprimaryandmetastaticbrainmalignancies.TheuniquepropertiesofthisorganrequireaspecificframeworkfordesigningTME-targetedinterventions.Here,wediscussanumberofthesedistinctfeatures,includingbrain-residentcelltypes,theblood-brainbarrier,andvariousaspectsoftheimmune-suppressiveenvironment.WealsohighlightrecentadvancesintherapeuticallytargetingthebrainTMEincancer.Bydevelopingacomprehensiveunderstandingofthecomplexandinterconnectedmicroenvironmentallandscapeofbrainma-lignancieswewillgreatlyexpandtherangeoftherapeuticstrategiesavailabletotargetthesedeadlydiseases.IntroductionThetumormicroenvironment(TME)containsmanydifferentnon-cancerouscelltypesinadditiontocancercells,includingendo-thelialcells,pericytes,fibroblasts,andimmunecells(QuailandJoyce,2013).Whileseveralofthesecelltypesarealsoprevalentinbraintumors,therearesomeimportantfeaturesthatdistinguishthenormalbrainfromothertissues;thecompositionoftheextra-cellularmatrix(ECM)isdistinctive,thereareuniquetissue-resi-dentcelltypesincludingmicroglia,astrocytesandneurons,anditisphysicallyprotectedfrominflammationbytheblood-brainbarrier(BBB).Indeed,thenormalbrainwaslongconsideredtobeoneofthe‘‘immuneprivileged’’organsinthebodythatmustbeshelteredfromimmunecellentryand/orattackforanumberofreasons(Engelhardtetal.,2017;Medawar,1948).Forinstance,activatedimmunecellsproduceinflammatoryfactorsthatcanbecytotoxicandcauseneurodegeneration.Inaddition,theskullpro-videsaphysicalbarriertotheswellingthatoftencoincideswit...
