Gene expression in murine pancreatic tumor tissues in response to the blockade of macrophage colony-stimulating factor receptor (CSF1R) signal
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE57686 | GEO | 2014/05/15
SECONDARY ACCESSION(S): PRJNA247690
REPOSITORIES: GEO
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Project description:Analysis of responses induced upon the blockade of CSF1R signaling at the gene expression level. Hypothesis of this study was that CSF1R signal blockade alters the local immune responses in a murine pancreatic tumor model. Results provide important information on changes in the immune responses in the tumor microenvironment. Total RNA obtained from whole mouse pancreatic tumor tissues after vehicle or CSF1Ri treatment for 8 days
2014-05-15 | E-GEOD-57686 | biostudies-arrayexpress
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
Project description:Chronic graft-versus-host disease (cGVHD) remains a significant complication of allogeneic hematopoietic stem cell transplantation. Central nervous system (CNS) involvement is becoming increasingly recognised, where brain-infiltrating donor MHC class II+ bone marrow-derived macrophages (BMDM) drive pathology. BMDM are also mediators of cutaneous and pulmonary cGVHD, and clinical trials assessing the efficacy of antibody blockade of colony-stimulating factor 1 receptor (CSF1R) to deplete macrophages are promising. We hypothesised that CSF1R antibody blockade may also be a useful strategy to prevent/treat CNS cGVHD. Increased blood-brain barrier permeability during acute GVHD (aGVHD) facilitated CNS antibody access and microglia depletion by anti-CSF1R treatment. However, CSF1R blockade early post-transplant unexpectedly exacerbated aGVHD neuroinflammation. In established cGVHD, vascular changes and anti-CSF1R efficacy were more limited. Anti-CSF1R-treated mice retained donor BMDM, activated microglia, CD8+ and CD4+ T cells, and local cytokine expression in the brain. These findings were recapitulated in GVHD recipients where CSF1R was conditionally depleted in donor CX3CR1+ BMDM. Notably, inhibition of CSF1R signalling post-transplant failed to reverse GVHD-induced behavioural changes. Moreover, we observed aberrant behaviour in non-GVHD control recipients administered anti-CSF1R blocking antibody and naïve mice lacking CSF1R in CX3CR1+ cells, revealing a novel role for homeostatic microglia and indicating that ongoing clinical trials of CSF1R inhibition should assess neurological adverse events in patients. In contrast, transfer of Ifngr-/- grafts could reduce MHC class II+ BMDM infiltration, resulting in improved neurocognitive function. Our findings highlight unexpected neurological immune toxicity during CSF1R blockade and provide alternative targets for the treatment of cGVHD within the CNS.
2023-10-18 | GSE245360 | GEO
Project description:Colony-stimulating factor 1 receptor (CSF1R) signaling controls MФ differentiation and function, and blocking CSF1R exerts antitumor effects in solid tumors. We examined the effects of CSF1R blockade on multiple therapy. Our results showed that CSF1R blockade inhibited the differentiation, proliferation and survival of M2 and myeloma-associated MФs (MAMs). Microarray was used for determining CS7 effect on polarization of MAMs. We used microarrays to detail the global programme of gene expression underlying polarizaiton of myeloma-associated macrophages by CSF1R antibody treatment and identified distinct classes of polarization-related genes during this process.
2017-06-30 | GSE99393 | GEO
Project description:Purpose: Colony-stimulating factor 1 receptor (CSF1R), a tyrosine kinase receptor, is a key regulator in the proliferation, differentiation, migration and colonization of macrophage lineage cells. Under pathological conditions, CSF1R was not only involved in the pathogenesis of immune disorders and hematopoietic diseases, but also closely related to tissue damage and tumor growth and metastasis. Therefore, comprehensive understanding of CSF1R function is of great significance. Methods: In this study, a csf1ra−/− zebrafish mutant line was generated using clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) technology. Results:The csf1ra−/− larvae were lack of the yellow cast on the head and over the flank, while the adult mutants had poorly formed stripes. The RNA-sequence analysis revealed that genes related to bile acid secretion, fat digestion and absorption and pancreatic secretion were differentially expressed in csf1ra−/− mutants, leading to the fatty change in the liver. Besides, genes related to locomotion were also significantly changed with more active movement in csf1ra−/− larvae and adults. Conclusions: Overall, our data reveal that csf1ra participates the metabolic process and behavior. This study provides new insight into the functions of csf1ra gene during the development in zebrafish.
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| S-EPMC5514481 | biostudies-literature
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.
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Project description:Immune checkpoint blockade is able to achieve durable responses in a subset of patients, however we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4 and anti-PD-1 induced tumor rejection. To address these issues we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor infiltrating T cell populations. Anti-PD-1 predominantly induces the expansion of specific tumor infiltrating exhausted-like CD8 T cell subsets. In contrast, anti-CTLA-4 induces the expansion of an ICOS+ Th1-like CD4 effector population in addition to engaging specific subsets of exhausted-like CD8 T cells. Thus, our findings indicate that anti-CTLA-4 and anti-PD-1 checkpoint blockade induced immune responses are driven by distinct cellular mechanisms.
2017-08-10 | GSE100808 | GEO
Project description:Immune checkpoint blockade is able to achieve durable responses in a subset of patients, however we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4 and anti-PD-1 induced tumor rejection. To address these issues we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor infiltrating T cell populations. Anti-PD-1 predominantly induces the expansion of specific tumor infiltrating exhausted-like CD8 T cell subsets. In contrast, anti-CTLA-4 induces the expansion of an ICOS+ Th1-like CD4 effector population in addition to engaging specific subsets of exhausted-like CD8 T cells. Thus, our findings indicate that anti-CTLA-4 and anti-PD-1 checkpoint blockade induced immune responses are driven by distinct cellular mechanisms.
2017-08-10 | GSE100807 | GEO
Project description:Single cell sequence (SC-seq) has been used to explore the effect of IL10/CSF1R fusion protein modulation in tumor microenvironment. Four groups were analyzed which contain Ctrl, CSF1R, IL10 and BF10. MTC-Q1 oral cancer cells were orthotopic injection in C57BL/6 mice. CD45+ immune cells has been isolated, analyzed and sequenced by dropped based scRNA-seq, cDNA were sequenced by Illumina Novaseq 6000.
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