Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

B-cell derived macrophage in mouse and human breast cancer macrophage

ABSTRACT: Cancer actively uses B cells to promote its progression and metastasis. For example, it causes accumulation of bone marrow (BM) B-cell precursors in spleen to convert into immunosuppressive Breg cells. Here, we provide evidence that cancer also coopts differentiation BM CSF1R+ Pax5Lo B-cell precursors to generate macrophages (termed B-MF cells). To do this, cancer uses CSF1 to trigger Csf1r signaling and downregulate PAX5 in B-cell precursors by activating FOXO1. Although tumor-associated macrophages (TAMs) are primarily derived from BM monocytes, our data suggest that some of them may have B-cell origin. Unlike monocyte-derived TAMs, B-MF exhibit a higher M2 polarization, more efficiently phagocytize apoptotic cells, induce FoxP3+ Tregs and suppress T cells activity. We propose that the cancer-B-MF axis is a novel immune escape pathway, thus a therapeutic target.

ORGANISM(S): Mus musculus

PROVIDER: GSE178716 | GEO | 2021/09/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Cancer coopts differentiation of B-cell precursors into macrophages [human]

Project description:We recently reported that some cancers induce accumulation of bone marrow (BM) B-cell precursors in the spleen to convert them into metastasis-promoting, immunosuppressive B cells. Here, using various murine tumor models and samples from humans with breast and ovarian cancers, we provide evidence that cancer cells also coopt differentiation of the extranodal B-cell precursors to generate macrophages (termed B-MF). We link the trans-differentiation to a small subset of CSF1R+ Pax5Lo cells within BM pro-/pre-B and immature B cells and cancer-secreted M-CSF that downregulates Pax5 via CSF1R signaling. Thus, cancer generates tumor-associated macrophages (TAM) from B-cell precursors besides their primary source, monocytes. Based on their differences from monocyte-derived TAM, such as a superb ability to induce FoxP3+ Tregs, suppress proliferation of T cells and more efficiently phagocytize apoptotic cells, we propose that cancer generates B-MF to mediate cancer escape.

2021-09-20 | GSE180284 | GEO

Cancer coopts differentiation of B-cell precursors into macrophages [mouse]

2021-09-20 | GSE180283 | GEO

Effect of CSF1R inhibition in tumor macrophages on gene expression in metastatic epithelial cells

Project description:Metastasis is the primary cause of mortality in breast cancer patients. Tumor associated macrophages (TAMs) are active collaborators in mediating several steps of the tumor metastatic cascade, but the molecular details governing this collaboration remain ill-defined. Colony Stimulating Factor 1 (CSF1), a factor critical for macrophage differentiation and survival, functions to recruit TAMs to the primary tumor site, and anti-CSF1 therapies are in clinical trials.In this study, we tested the effect of inhibiting CSF1 signaling in macrophages on gene expression in metastatic tumor cells in mouse models of breast cancer metastasis. Tumor cells were sorted from lung metastases from control and CSF1R inhibitor treated mice. Several pro-tumor processes were significantly affected by CSF1R inhibitor treatment, including angiogenesis and tumor cell proliferation. In addition, a 29 gene signature derived from this data could retrospectively predict survival in a cohort of luminal B breast cancer patients. Collectievly, our results highlight the utility of employing CSF1R inhibitors for the treatment of metastatic breast cancer. GFP tagged MVT1 metastatic mammary tumor cells were injected intravenously into FVB/N mice. Mice were gavaged with the CSF1R inhibitor GW2580 or vehicle starting one week post injection. GFP tagged tumor cells were sorted from metastatic tumor bearing lungs 1 and 2 weeks post injection from 2 vehicle treated mice for each. These are denoted 1_week_WT and 2_week_WT respectively. GFP tagged tumor cells were simultaneously sorted from mice gavaged with GW2580. These samples are denoted 2_week_GW. RNA was extracted and gene expression profiling was performed using the Affymetrix Mouse Genome 430 2.0 Array platform.

2014-03-13 | E-GEOD-55855 | biostudies-arrayexpress

Compensatory Csf2-driven macrophage activation blunts long-term efficacy of therapeutic Csf1r inhibition in breast-to-brain metastasis

Project description:Tumor microenvironment-targeted therapies are emerging as promising treatment options for different tumor types. Tumor-associated macrophages/microglia (TAMs) represent the most abundant non-malignant cell type in brain metastasis and are known to support metastatic colonization and outgrowth. We used the colony-stimulating factor 1 receptor (Csf1r) inhibitor BLZ945 to target TAMs at distinct stages of the metastatic cascade in experimental breast-to-brain metastasis and demonstrate that Csf1r inhibition leads to anti-tumor responses in prevention and intervention trails. However, compensatory Csf2-mediated pro-inflammatory TAM activation blunts long-term efficacy of Csf1r inhibition by inducing signatures associated with neuroinflammation followed by wound repair responses that foster tumor recurrence. Combined blockade of Csf1r and Csf2rb-Stat5 signaling leads to sustained tumor control and a normalization of microglial activation states.

2019-12-06 | GSE133887 | GEO

Transcriptome-based profiling reveals a macrophage pedigree and identifies Irf8 as pivotal for macrophage homeostasis and function

Project description:Recent studies have shown that tissue macrophages (MF) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize the tissues before birth. Further studies have proposed that developmentally distinct tissue MF can be identified based on the differential expression of F4/80 and CD11b, but whether a characteristic transcriptional profile exists is largely unknown. Here, we established an inducible fate mapping system that facilitated the identification of A2 progenitors of the YS as source of F4/80hi but not CD11bhi MF. Large-scale transcriptional profiling of MF precursors from the YS until adulthood allowed the description of a complex MF pedigree. We further identified a distinct molecular signature of F4/80hi and CD11bhi MF and found that Irf8 was vital for MF maturation and the innate immune response. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MF. All samples are from mouse tissue at early developmental stages (E8, E9.5, E14) and from adulthood (6 weeks old). For the early developmental time points timed matings were performed. Macrophage populations were isolated from each tissue. RNA was isolated using Arcturus PicoPure isolation kit from yolk sac, brain, liver, kidney and skin samples after FACS sorting. Three replicates per cell population were included. Wildtype and Irf8 knockout samples were analyzed.

2016-07-28 | E-GEOD-73125 | biostudies-arrayexpress

Transcriptome-based profiling reveals a macrophage pedigree and identifies Irf8 as pivotal for macrophage homeostasis and function

2016-07-28 | GSE73125 | GEO

Cancer coopts differentiation of B-cell precursors into macrophages

Project description:Cancer coopts differentiation of B-cell precursors into macrophages

| PRJNA747688 | ENA

Cancer coopts differentiation of B-cell precursors into macrophages [mouse]

Project description:Cancer coopts differentiation of B-cell precursors into macrophages [mouse]

| PRJNA747690 | ENA

Cancer coopts differentiation of B-cell precursors into macrophages [human]

Project description:Cancer coopts differentiation of B-cell precursors into macrophages [human]

| PRJNA747692 | ENA