Characterization of tumor associated macrophages (TAM) in the tumor microenvironment of human melanoma
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PROVIDER: PRJNA718886 | ENA |
REPOSITORIES: ENA
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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.
2021-08-09 | GSE171277 | GEO
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.
2021-11-12 | GSE188549 | GEO
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.
2015-03-31 | E-GEOD-67408 | biostudies-arrayexpress
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.
2023-10-30 | PXD046492 | iProX
Project description:Transcriptional Characterization of the Tumor Microenvironment and Prognostic Gene Signatures in Conjunctival Melanoma
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Project description:Profiling of tumor-associated macrophages (TAM) after anti-MerTK treatment
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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
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
2015-03-31 | GSE67408 | GEO
Project description:Gene expression was analyzed in peritoneal macrophages and TAM from mice injected with ID8 ovarian cancer cells intraperitoneally 5 and 21 days after tumor cell injection. Tumor-associated macrophages (TAM) have been shown to have important roles in the malignant progression of various cancers. However, macrophages also posses intrinsic tumoricidal activity and can promote the activity of cytotoxic lymphocytes, but they rapidly adopt an alternative phenotype within tumors, associated with immune-suppression and trophic functions that support tumor growth. The mechanisms that promote TAM polarization in the tumor-microenvironment remain poorly understood, these mechanisms may represent important therapeutic targets to block the tumor-promoting functions of TAM and restore their anti-tumor potential. Here we have characterized TAM in a mouse model of metastatic ovarian cancer. We show that ovarian cancer cells promote membrane-cholesterol efflux and the depletion of lipid rafts from macrophages. Increased cholesterol efflux promoted IL-4 mediated reprogramming while inhibiting IFNg-induced gene expression. These studies reveal an unexpected role for tumor-induced membrane-cholesterol efflux in driving the IL-4 signaling and the tumor-promoting functions of TAM, while rendering them refractory to pro-inflammatory stimuli. Thus, preventing cholesterol efflux in TAM could represent a novel therapeutic strategy to block pro-tumor functions and restore anti-tumor immunity.
2019-02-06 | GSE126098 | GEO
Project description:Purpose: To characterize the transcriptome and cellular the tumor microenvi-ronment of conjunctival melanoma (CM) compared to healthy conjunctiva and to analyze the transcriptional differences between CM with good and poor clinical outcome. Methods: Twelve formalin-fixed and paraffin-embedded (FFPE) CM of twelve patients were analyzed by Massive Analysis of cDNA Ends (MACE) RNA se-quencing. Six samples each with good and poor clinical outcome were exam-ined, the latter being defined by local recurrence or systemic metastases with a follow-up of at least 24 months. Eight age-matched healthy FFPE conjunctival specimens from eight patients who underwent retinal detachment surgery served as controls. Bioinformatic cell type enrichment analysis with xCell was used to characterize the tumor microenvironment (TME). Differentially expressed genes (DEG) and the associated biological processes were analyzed between CM and control conjunctiva. Additionally, a prognostic transcription profile was identified by comparing melanoma of good and poor clinical outcome. Results: The TME of conjunctival melanoma was characterized by the enrich-ment of melanocytes, pericytes and especially several immune cell types. Among them, plasmacytoid dendritic cells (pDC), natural killer T cells (NKT), B cells and mast cells were most significantly increased in CM compared to healthy conjunc-tiva. DEG between CM and control were mainly involved in biological processes such as inhibition of apoptosis, proteolysis and response to growth factors. POU3F3, BIRC5 and 7 were among the top expressed genes associated with inhibition of apoptosis. Twenty genes, among them CENPK, INHA, USP33 and CASP3, were identified as prognostically relevant factors reaching high classifi-cation accuracy (AUC: 1.0). Conclusions: The present study provides new insights into the TME and the transcriptional profile of CM and additionally identifies new prognostic bi-omarkers. These results might lead to new diagnostic and therapeutic options for CM.
2020-08-30 | GSE148387 | GEO