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CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10.
Guldner, Ian H; Wang, Qingfei; Yang, Lin; Golomb, Samantha M; Zhao, Zhuo; Lopez, Jacqueline A; Brunory, Abigail; Howe, Erin N; Zhang, Yizhe; Palakurthi, Bhavana; Barron, Martin; Gao, Hongyu; Xuei, Xiaoling; Liu, Yunlong; Li, Jun; Chen, Danny Z; Landreth, Gary E; Zhang, Siyuan.
Afiliação
  • Guldner IH; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA.
  • Wang Q; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA.
  • Yang L; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA; Department of Computer Science and Engineering, College of Engineering, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Golomb SM; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA.
  • Zhao Z; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA; Department of Computer Science and Engineering, College of Engineering, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Lopez JA; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Brunory A; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA.
  • Howe EN; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA.
  • Zhang Y; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA; Department of Computer Science and Engineering, College of Engineering, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Palakurthi B; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA.
  • Barron M; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA; Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Gao H; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN 46202, USA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA.
  • Xuei X; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN 46202, USA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA.
  • Liu Y; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN 46202, USA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA.
  • Li J; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA; Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Chen DZ; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA; Department of Computer Science and Engineering, College of Engineering, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Landreth GE; Indiana University School of Medicine Stark Neuroscience Research Institute, Indianapolis, IN 46202, USA.
  • Zhang S; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA. Elect
Cell ; 183(5): 1234-1248.e25, 2020 11 25.
Article em En | MEDLINE | ID: mdl-33113353
ABSTRACT
Brain metastasis (br-met) develops in an immunologically unique br-met niche. Central nervous system-native myeloid cells (CNS-myeloids) and bone-marrow-derived myeloid cells (BMDMs) cooperatively regulate brain immunity. The phenotypic heterogeneity and specific roles of these myeloid subsets in shaping the br-met niche to regulate br-met outgrowth have not been fully revealed. Applying multimodal single-cell analyses, we elucidated a heterogeneous but spatially defined CNS-myeloid response during br-met outgrowth. We found Ccr2+ BMDMs minimally influenced br-met while CNS-myeloid promoted br-met outgrowth. Additionally, br-met-associated CNS-myeloid exhibited downregulation of Cx3cr1. Cx3cr1 knockout in CNS-myeloid increased br-met incidence, leading to an enriched interferon response signature and Cxcl10 upregulation. Significantly, neutralization of Cxcl10 reduced br-met, while rCxcl10 increased br-met and recruited VISTAHi PD-L1+ CNS-myeloid to br-met lesions. Inhibiting VISTA- and PD-L1-signaling relieved immune suppression and reduced br-met burden. Our results demonstrate that loss of Cx3cr1 in CNS-myeloid triggers a Cxcl10-mediated vicious cycle, cultivating a br-met-promoting, immune-suppressive niche.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Terapia de Imunossupressão / Células Mieloides / Quimiocina CXCL10 Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Terapia de Imunossupressão / Células Mieloides / Quimiocina CXCL10 Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article