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@ARTICLE{Li:293326,
author = {Z.-J. Li and B. He and A. Domenichini and J. Satiaputra and
K. H. Wood and D. D. Lakhiani and A. A. Bashaw and L. M.
Nilsson and J. Li and E. R. Bastow and A. Johansson-Percival
and E. Denisenko and A. R. Forrest and S. Sakaram and R.
Carretero$^*$ and G. J. Hämmerling$^*$ and J. A. Nilsson
and G. Y. Lee and R. Ganss},
title = {{P}ericyte phenotype switching alleviates immunosuppression
and sensitizes vascularized tumors to immunotherapy in
preclinical models.},
journal = {The journal of clinical investigation},
volume = {134},
number = {18},
issn = {0021-9738},
address = {Ann Arbor, Mich.},
publisher = {ASCJ},
reportid = {DKFZ-2024-01876},
pages = {e179860},
year = {2024},
abstract = {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.},
keywords = {Animals / Pericytes: immunology / Pericytes: metabolism /
Pericytes: pathology / Mice / Humans / Tumor
Microenvironment: immunology / Tumor Microenvironment: drug
effects / Immunotherapy / Melanoma, Experimental: immunology
/ Melanoma, Experimental: therapy / Melanoma, Experimental:
pathology / Phenotype / Melanoma: immunology / Melanoma:
therapy / Melanoma: pathology / Melanoma: drug therapy /
Cell Line, Tumor / Immune Tolerance: drug effects / Cancer
immunotherapy (Other) / Mouse models (Other) / Oncology
(Other) / Pericytes (Other) / Therapeutics (Other)},
cin = {D220 / D470},
ddc = {610},
cid = {I:(DE-He78)D220-20160331 / I:(DE-He78)D470-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39286984},
doi = {10.1172/JCI179860},
url = {https://inrepo02.dkfz.de/record/293326},
}