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Characterization of tumor associated macrophages (TAM) in the tumor microenvironment of human melanoma

ABSTRACT: Characterization of tumor associated macrophages (TAM) in the tumor microenvironment of human melanoma

PROVIDER: PRJNA718886 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14121837.fastq.gz	Fastqsanger.gz
	SRR14121838.fastq.gz	Fastqsanger.gz
	SRR14121839.fastq.gz	Fastqsanger.gz
	SRR14121840.fastq.gz	Fastqsanger.gz
	SRR14121841.fastq.gz	Fastqsanger.gz

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Characterization of tumor associated macrophages (TAM) in the tumor microenvironment of human melanoma

Project description:Tumor cells attract and dynamically interact with monocytes/macrophages to subvert their differentiation into tumor associated macrophages (TAMs), which mainly promote immunosuppression and neoplastic progression, but the pathways and microenvironmental cues governing their protumoral deviation are not completely understood. Thus, identifying molecular pathways responsible for TAM differentiation may provide new therapeutic targets to improve the efficacy of immunotherapy of cancer.

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microRNA expression during tumor-associated macrophage (TAM) differentiation

Project description:To further analyze the change of microRNA(miRNA) between normal peritoneal macrophage(PEC) and TAM from early tumor(12 days after 4T1 cell injection) or TAM from late tumor(21 days after 4T1 cell injection) , we employed Agilent mouse microRNA microarray Rel 12.0 as a discovery platform to identify miRNAs Total RNA from peritoneal macrophage and TAM of early tumor (tumor formed for 12days after BALB/c mice injected wth 4T1 cell) or TAM of late tumor(tumor formed for 21days after BALB/c mice injected with 4T1 cell) were extracted and analyzed using Agilent mouse microRNA microarray platform, and changes of miRNA were screened out. Agilent mouse microRNA microarray is designed for the profiling of mouse miRNA .627 mouse miRNA and 39 mouse virus-related miRNA can be detected by our microRNA microarray.

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Macrophages are metabolically heterogenous within the tumor microenvironment

Project description:Macrophages are often prominently present in the tumor microenvironment, where distinct macrophage populations can differentially affect tumor progression. Although metabolism influences macrophage function, studies on the metabolic characteristics of ex vivo tumor-associated macrophage (TAM) subsets are rather limited. Using transcriptomic and metabolomic analyses, we now reveal that pro-inflammatory MHC-IIhi TAMs display a hampered TCA cycle, while reparative MHC-IIlo TAMs show a higher oxidative and glycolytic metabolism. Although both TAM subsets rapidly exchange lactate in high lactate conditions, only MHC-IIlo TAMs use lactate as an additional carbon source. Accordingly, lactate supports the oxidative metabolism in MHC-IIlo TAMs, while it decreased the metabolic activity of MHC-IIhi TAMs. Lactate subtly affected the transcriptome of MHC-IIlo TAMs, increased L-arginine metabolism and enhanced T-cell suppressive capacity of these TAMs. Overall, our data uncover the metabolic intricacies of distinct TAM subsets and identify lactate as a carbon source, and metabolic and functional regulator of TAMs.

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A Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-associated Macrophages and Their Precursor Cells in Tumor Progression

Project description:Tumor-associated macrophages (TAMs) are key regulators in tumor progression. Although a role of bone marrow-derived monocytes (Mons) as TAM precursors has been revealed, the dynamic phenotypes of both TAMs and Mons regulated by the tumor microenvironment remain unclear. Here, we constructed an optimized micro-proteomics workflow, which was applicable to the mouse myeloid cells of low cell number. We sorted both TAMs and the corresponding Mons (1×105 per sample) from individual melanoma mouse model in the early stage and the late stage to establish the protein expression profiles by mass spectrum.

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ZDHHC13 Modulates Tumor Microenvironment Interactions to Suppress Melanoma Metastasis [scRNA-Seq]

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Transcriptional Characterization of the Tumor Microenvironment and Prognostic Gene Signatures in Conjunctival Melanoma

Project description:Transcriptional Characterization of the Tumor Microenvironment and Prognostic Gene Signatures in Conjunctival Melanoma

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Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases

Project description:Type I interferons (IFNs) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies by activating both innate and adaptive intratumoral immune cell populations. Macrophages are one of the most abundant innate immune cells in the immune microenvironment of melanoma brain metastases (MBMs) and can exert potent immune-suppressive functions. Here, we investigate the potential of tumoral type I IFNs to re-polarize tumor-associated macrophages (TAMs) in a murine melanoma mouse model. We describe a pro-inflammatory and M1-like TAM phenotype induced by tumoral IFNβ and identify a myeloid type I interferon-response signature associated with a high M1/M2 TAM ratio and an increased overall survival in previously irradiated patients with MBMs. We provide evidence that tumoral IFNβ supports an effective antitumor immune response by re-educating immune-regulatory TAMs. These findings uncover type I interferon-dependent therapies as a potential macrophage-targeting therapeutic approach and provide a rationale for combining radiotherapy with concomitant immunotherapy to improve treatment response in patients with MBM.

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Profiling of tumor-associated macrophages (TAM) after anti-MerTK treatment

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Comparison of Invasive TAM sub-population to General TAM population

Project description:The tumor microenvironment modifies the malignancy of tumors. In solid tumors this environment is populated by many macrophages (tumor-associated macrophages; TAMs) that in genetic studies that depleted these cells from mouse models of breast cancer were shown to promote tumor progression to malignancy and increase metastatic potential. Mechanistic studies showed that these effects are through the stimulation of tumor cell migration, invasion, intravasation as well as an enhancement of angiogenesis. Using an in vivo invasion assay it was demonstrated that invasive carcinoma cells are a unique sub-population of tumor cells whose invasion and chemotaxis is dependent upon the co-migration of TAMs with obligate reciprocal signaling through an EGF/CSF-1 paracrine loop. In this study these invasion-promoting macrophages were isolated and subjected to analysis of their transcriptome in comparison to TAMs isolated indiscriminately to function using established macrophage markers by flow cytometry. Five biological replicates for each population (Invasive and General TAM) were used.

2010-05-16 | E-GEOD-18295 | biostudies-arrayexpress

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