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000293326 1001_ $$aLi, Zhi-Jie$$b0
000293326 245__ $$aPericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models.
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000293326 520__ $$aT cell-based immunotherapies are a promising therapeutic approach for multiple malignancies, but their efficacy is limited by tumor hypoxia arising from dysfunctional blood vessels. Here, we report that cell-intrinsic properties of a single vascular component, namely the pericyte, contribute to the control of tumor oxygenation, macrophage polarization, vessel inflammation, and T cell infiltration. Switching pericyte phenotype from a synthetic to a differentiated state reverses immune suppression and sensitizes tumors to adoptive T cell therapy, leading to regression of melanoma in mice. In melanoma patients, improved survival is correlated with enhanced pericyte maturity. Importantly, pericyte plasticity is regulated by signaling pathways converging on Rho kinase activity, with pericyte maturity being inducible by selective low-dose therapeutics that suppress pericyte MEK, AKT, or notch signaling. We also show that low-dose targeted anticancer therapy can durably change the tumor microenvironment without inducing adaptive resistance, creating a highly translatable pathway for redosing anticancer targeted therapies in combination with immunotherapy to improve outcome.
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000293326 650_7 $$2Other$$aCancer immunotherapy
000293326 650_7 $$2Other$$aMouse models
000293326 650_7 $$2Other$$aOncology
000293326 650_7 $$2Other$$aPericytes
000293326 650_7 $$2Other$$aTherapeutics
000293326 650_2 $$2MeSH$$aAnimals
000293326 650_2 $$2MeSH$$aPericytes: immunology
000293326 650_2 $$2MeSH$$aPericytes: metabolism
000293326 650_2 $$2MeSH$$aPericytes: pathology
000293326 650_2 $$2MeSH$$aMice
000293326 650_2 $$2MeSH$$aHumans
000293326 650_2 $$2MeSH$$aTumor Microenvironment: immunology
000293326 650_2 $$2MeSH$$aTumor Microenvironment: drug effects
000293326 650_2 $$2MeSH$$aImmunotherapy
000293326 650_2 $$2MeSH$$aMelanoma, Experimental: immunology
000293326 650_2 $$2MeSH$$aMelanoma, Experimental: therapy
000293326 650_2 $$2MeSH$$aMelanoma, Experimental: pathology
000293326 650_2 $$2MeSH$$aPhenotype
000293326 650_2 $$2MeSH$$aMelanoma: immunology
000293326 650_2 $$2MeSH$$aMelanoma: therapy
000293326 650_2 $$2MeSH$$aMelanoma: pathology
000293326 650_2 $$2MeSH$$aMelanoma: drug therapy
000293326 650_2 $$2MeSH$$aCell Line, Tumor
000293326 650_2 $$2MeSH$$aImmune Tolerance: drug effects
000293326 7001_ $$aHe, Bo$$b1
000293326 7001_ $$aDomenichini, Alice$$b2
000293326 7001_ $$aSatiaputra, Jiulia$$b3
000293326 7001_ $$aWood, Kira H$$b4
000293326 7001_ $$aLakhiani, Devina D$$b5
000293326 7001_ $$aBashaw, Abate A$$b6
000293326 7001_ $$aNilsson, Lisa M$$b7
000293326 7001_ $$aLi, Ji$$b8
000293326 7001_ $$aBastow, Edward R$$b9
000293326 7001_ $$aJohansson-Percival, Anna$$b10
000293326 7001_ $$aDenisenko, Elena$$b11
000293326 7001_ $$aForrest, Alistair Rr$$b12
000293326 7001_ $$aSakaram, Suraj$$b13
000293326 7001_ $$0P:(DE-He78)86723b26e79aa190a6c7294651a80986$$aCarretero, Rafael$$b14$$udkfz
000293326 7001_ $$0P:(DE-He78)5f9901fc60b769b523d0dd8e79b3fe08$$aHämmerling, Günter J$$b15$$udkfz
000293326 7001_ $$aNilsson, Jonas A$$b16
000293326 7001_ $$aLee, Gabriel Yf$$b17
000293326 7001_ $$aGanss, Ruth$$b18
000293326 773__ $$0PERI:(DE-600)2018375-6$$a10.1172/JCI179860$$gVol. 134, no. 18, p. e179860$$n18$$pe179860$$tThe journal of clinical investigation$$v134$$x0021-9738$$y2024
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