Home > Publications database > Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models. > print

001     293326
005     20240922012816.0
024 7 _ |a 10.1172/JCI179860
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082 _ _ |a 610
100 1 _ |a Li, Zhi-Jie
|b 0
245 _ _ |a Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models.
260 _ _ |a Ann Arbor, Mich.
|c 2024
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520 _ _ |a T 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.
536 _ _ |a 314 - Immunologie und Krebs (POF4-314)
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650 _ 7 |a Cancer immunotherapy
|2 Other
650 _ 7 |a Mouse models
|2 Other
650 _ 7 |a Oncology
|2 Other
650 _ 7 |a Pericytes
|2 Other
650 _ 7 |a Therapeutics
|2 Other
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Pericytes: immunology
|2 MeSH
650 _ 2 |a Pericytes: metabolism
|2 MeSH
650 _ 2 |a Pericytes: pathology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Tumor Microenvironment: immunology
|2 MeSH
650 _ 2 |a Tumor Microenvironment: drug effects
|2 MeSH
650 _ 2 |a Immunotherapy
|2 MeSH
650 _ 2 |a Melanoma, Experimental: immunology
|2 MeSH
650 _ 2 |a Melanoma, Experimental: therapy
|2 MeSH
650 _ 2 |a Melanoma, Experimental: pathology
|2 MeSH
650 _ 2 |a Phenotype
|2 MeSH
650 _ 2 |a Melanoma: immunology
|2 MeSH
650 _ 2 |a Melanoma: therapy
|2 MeSH
650 _ 2 |a Melanoma: pathology
|2 MeSH
650 _ 2 |a Melanoma: drug therapy
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Immune Tolerance: drug effects
|2 MeSH
700 1 _ |a He, Bo
|b 1
700 1 _ |a Domenichini, Alice
|b 2
700 1 _ |a Satiaputra, Jiulia
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700 1 _ |a Wood, Kira H
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700 1 _ |a Lakhiani, Devina D
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700 1 _ |a Bashaw, Abate A
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700 1 _ |a Nilsson, Lisa M
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700 1 _ |a Li, Ji
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700 1 _ |a Bastow, Edward R
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700 1 _ |a Johansson-Percival, Anna
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700 1 _ |a Denisenko, Elena
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700 1 _ |a Forrest, Alistair Rr
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700 1 _ |a Sakaram, Suraj
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700 1 _ |a Carretero, Rafael
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700 1 _ |a Hämmerling, Günter J
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700 1 _ |a Nilsson, Jonas A
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700 1 _ |a Lee, Gabriel Yf
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700 1 _ |a Ganss, Ruth
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773 _ _ |a 10.1172/JCI179860
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