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.
Pubmed ID: 33113353 RIS Download
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Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
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View all literature mentionsSoftware package for analysis of expression dynamics in single cell RNA seq data. Enables estimations of RNA velocities of single cells by distinguishing unspliced and spliced mRNAs in standard single-cell RNA sequencing protocols. Estimates RNA velocity in single cell RNA sequencing datasets. RNA velocity estimation in Python or R.
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View all literature mentionsThis monoclonal targets PD-L1 (B7-H1)
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View all literature mentionsThis monoclonal targets CD183
View all literature mentionsThis monoclonal targets I-A/I-E
View all literature mentionsThis monoclonal targets NK-1.1
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets Ly-6G Ly-6C
View all literature mentionsThis monoclonal targets Ly-6C
View all literature mentionsThis monoclonal targets Ly-6C
View all literature mentionsThis monoclonal targets Ly-6C
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets H-2/CD45
View all literature mentionsThis monoclonal targets H-2/CD45
View all literature mentionsThis monoclonal targets H-2/CD45
View all literature mentionsThis monoclonal targets H-2/CD45
View all literature mentionsThis monoclonal targets H-2/CD45
View all literature mentionsThis monoclonal targets H-2/CD45
View all literature mentionsThis monoclonal targets H-2/CD45
View all literature mentionsThis monoclonal targets H-2/CD45
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View all literature mentionsThis monoclonal targets XCR1
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View all literature mentionsThis monoclonal targets CD169
View all literature mentionsThis monoclonal targets CD274
View all literature mentionsThis monoclonal targets CD279
View all literature mentionsThis monoclonal targets NK-1.1
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets Ly-6C
View all literature mentionsThis monoclonal targets I-A/I-E
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis monoclonal targets CX3CR1
View all literature mentionsThis monoclonal targets CD90/CD90.1
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD86
View all literature mentionsThis monoclonal targets CD45R
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets CD44
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD38
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets CD25
View all literature mentionsThis monoclonal targets CD172a
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD117
View all literature mentionsThis monoclonal targets CD192
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD117/c-kit
View all literature mentionsThis monoclonal targets CX3CR1
View all literature mentionsThis monoclonal targets CD279/PD-1
View all literature mentionsThis monoclonal targets CD274/PD-L1
View all literature mentionsThis monoclonal targets CD3e
View all literature mentionsThis monoclonal targets CD25
View all literature mentionsThis monoclonal targets CD44
View all literature mentionsThis monoclonal targets CD11b/Mac-1
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD45R/B220
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis unknown targets Mouse IgG, Fc? Fragment Specific
View all literature mentionsThis unknown targets Guinea Pig IgG (H+L)
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG, Fc Fragment Specific
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis polyclonal targets Iba1
View all literature mentionsThis monoclonal targets VISTA
View all literature mentionsThis monoclonal targets TMEM119
View all literature mentionsThis polyclonal targets TMEM119
View all literature mentionsThis monoclonal targets mCherry
View all literature mentionsThis monoclonal targets CD3 antibody [SP7]
View all literature mentionsThis monoclonal targets Siglec H
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View all literature mentionsMus musculus with name B6.129(Cg)-Ccr2tm2.1Ifc/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2(Cg)-Cx3cr1tm1Litt/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6-Gt(ROSA)26Sortm1(HBEGF)Awai/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2(Cg)-Cx3cr1tm2.1(cre/ERT2)Litt/WganJ from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line SIM-A9 is a Spontaneously immortalized cell line with a species of origin Mus musculus
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