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Sustained inhibition of CSF1R signaling augments antitumor immunity through inhibiting tumor-associated macrophages

ABSTRACT: Sustained inhibition of CSF1R signaling augments antitumor immunity through inhibiting tumor-associated macrophages

PROVIDER: PRJNA1015572 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26038823_1.fastq.gz	Fastqsanger.gz
	SRR26038823_2.fastq.gz	Fastqsanger.gz
	SRR26038824_1.fastq.gz	Fastqsanger.gz
	SRR26038824_2.fastq.gz	Fastqsanger.gz
	SRR26038825_1.fastq.gz	Fastqsanger.gz

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Sustained inhibition of CSF1R signaling augments antitumor immunity through inhibiting tumor-associated macrophages

Project description:Tumor-associated macrophages (TAMs) are one of the key immunosuppressive components in the tumor microenvironment (TME) and contribute to tumor development, progression, and resistance to cancer immunotherapy. Several reagents targeting TAMs have been tested in preclinical and clinical studies, but they have had limited success. Here, we show that a unique reagent, FF-10101, exhibits a sustained inhibitory effect against colony stimulating factor 1 receptor by forming a covalent bond and reduces immunosuppressive TAMs in the TME, which leads to strong antitumor immunity. In preclinical animal models, FF-10101 treatment significantly reduced immunosuppressive TAMs and increased antitumor TAMs in the TME. In addition, tumor antigen-specific CD8+ T cells were increased; consequently, tumor growth was significantly inhibited. Moreover, combination treatment with an anti-PD-1 antibody and FF-10101 exhibited a far stronger antitumor effect than either treatment alone. In human cancer specimens, FF-10101 treatment reduced PD-L1 expression on TAMs, as observed in animal models. Thus, FF-10101 acts as an immunomodulatory agent that can reduce immunosuppressive TAMs and augment tumor antigen-specific T cell responses, thereby generating an immunostimulatory TME. We propose that FF-10101 is a potential candidate for successful combination cancer immunotherapy with immune checkpoint inhibitors, such as PD-1/PD-L1 blockade.

2025-01-15 | GSE242937 | GEO

Gene expression data of CSF1R antibody-treated myeloma-associated macrophages

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

Inhibiting tumor cell-intrinsic UBA6 by inosine augments tumor immunogenicity

Project description:Inhibiting tumor cell-intrinsic UBA6 by inosine augments tumor immunogenicity

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Targeting tumor-intrinsic S100A1 augments antitumor immunity and potentiates immunotherapy efficacy

Project description:Targeting tumor-intrinsic S100A1 augments antitumor immunity and potentiates immunotherapy efficacy

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Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement

Project description:Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement

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Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement [scRNAseq]

Project description:Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement [scRNAseq]

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Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement [ATACseq]

Project description:Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement [ATACseq]

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Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement [WGBS]

Project description:Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement [WGBS]

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Interleukin-10/CSF1R fusion protein rejuvenates the exhausted T cells for executing antitumor activity

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.

2023-07-09 | GSE190111 | 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

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