ResouRcehttps://doi.org/10.1038/s41591-018-0096-51VIBCenterforCancerBiology,Leuven,Belgium.2LaboratoryforTranslationalGenetics,DepartmentofHumanGenetics,KULeuven,Leuven,Belgium.3RespiratoryOncologyUnit(Pneumology)andLeuvenLungCancerGroup,UniversityHospitalsKULeuven,Leuven,Belgium.4LaboratoryofPneumology,DepartmentofChronicDiseases,MetabolismandAgeing,KULeuven,Leuven,Belgium.5LaboratoryforComputationalBiology,DepartmentofHumanGenetics,KULeuven,Leuven,Belgium.6VIB-KULeuvenCenterforBrain&DiseaseResearch,Leuven,Belgium.7HistopathologyExpertiseCenter,VIBLeuvenCenterforCancerBiology,VIB,Leuven,Belgium.8DepartmentofOncology,KULeuven,Leuven,Belgium.9LaboratoryofGeneticsofAutoimmunity,DepartmentofMicrobiologyandImmunology,KULeuven,Leuven,Belgium.10DepartmentofThoracicSurgery,UniversityHospitalsKULeuven,Leuven,Belgium.11DepartmentofChronicDiseases,MetabolismandAgeing,KULeuven,Leuven,Belgium.12LaboratoryofAngiogenesisandVascularMetabolism,DepartmentofOncology,KULeuven,Leuven,Belgium.13TranslationalCell&TissueResearch,DepartmentofImaging&Pathology,KULeuven,Leuven,Belgium.14StateKeyLaboratoryofOphthalmology,ZhongsanOphthalmicCenter,SunYat-SenUniversity,Guangzhou,China.15LaboratoryforFunctionalEpigenetics,DepartmentofHumanGenetics,KULeuven,Leuven,Belgium.*e-mail:diether.lambrechts@kuleuven.vib.be;bernard.thienpont@kuleuven.beTumorsarecharacterizedbyextensiveheterogeneity,butsofareffortsinunderstandingthisheterogeneitywerelargelylim-itedtocancercells1.Theserevealedaremarkablycomplexanddiverseportraitofcancercells,withevidenceforgeneticdiversifi-cationandclonalselection.However,thestromalcellsassociatedwithtumors,andthecomplexcellularecosystemtheybuildtoformtheTME,maythemselvesbeascomplexandheterogeneousasthecancercellcompartment2,3.Particularly,anincreasingnumberofstudiessuggestthatstromalcells,suchasmacrophages,Tcellsandfibroblasts,arehighlyheterogeneous4–7.Theextentofthishetero-geneity,howitisshapedbyothercellsinthetumorandviceversaalsodirectlyaffectsthem,remainshoweverpoorl...
