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Targeting PAK4 to reprogram the vascular

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Articleshttps://doi.org/10.1038/s43018-020-00147-81DepartmentofRadiationOncology,UniversityofPennsylvania,Philadelphia,PA,USA.2DepartmentofObstetricsandGynecology,UniversityofPennsylvania,Philadelphia,PA,USA.3DepartmentofNeurosurgery,UniversityofPennsylvania,Philadelphia,PA,USA.4GlioblastomaTranslationalCenterofExcellence,AbramsonCancerCenter,UniversityofPennsylvania,Philadelphia,PA,USA.5DepartmentofMicrobiology,UniversityofPennsylvania,Philadelphia,PA,USA.6CenterforCellularImmunotherapies,AbramsonCancerCenter,UniversityofPennsylvania,Philadelphia,PA,USA.7DivisionofTranslationalMedicineandHumanGenetics,DepartmentofMedicine,UniversityofPennsylvania,Philadelphia,PA,USA.8Presentaddress:StateKeyLaboratoryofOncologyinSouthChinaandCollaborativeInnovationCenterforCancerMedicine,SunYat-senUniversityCancerCenter,Guangzhou,China.9Theseauthorscontributedequally:WenjuanMa,YanlingWang,RongxinZhang,FanYang.10Theseauthorsjointlysupervisedthiswork:YanqingGong,YiFan.✉e-mail:gongy@pennmedicine.upenn.edu;yi.fan@pennmedicine.upenn.eduTcell-basedimmunotherapyforsolidtumorsiscur-rentlylimitedbyefficacychallenges,largelyduetotumormicroenvironment-dependenttherapeuticresistance.Thetumorvasculatureisstructurallyandtopologicallyabnormal,whichimpedesthedeliveryofTcellsintothetumor1–4.Moreover,tumor-associatedendothelialcells(ECs)withfunctionalabnormali-tiesinduceheterogeneoushypoxiaandformavascularnichethatinducesimmunesuppression5–9,furthercontributingtotumoreva-sionofimmuneresponsesandinducingtumorr

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