Project description:Sequencing of mRNA from tissue-resident and tumor-associated macrophages in murine omentum display distinct transcriptional profile between macrophage subset of different origin
Project description:The omentum is the most common site of ovarian cancer metastasis. Immune cell clusters called milky spots are found throughout the omentum. It is however unknown if these immune cells contribute to ovarian cancer metastasis. Here we report that omental macrophages promote the migration and colonization of ovarian cancer cells to the omentum through the secretion of chemokine ligands that interact with chemokine receptor 1 (CCR1). We found that depletion of macrophages reduces ovarian cancer colonization of the omentum. RNA-sequencing of macrophages isolated from mouse omentum and mesenteric adipose tissue revealed a specific enrichment of CCL6 chemokine ligand in omental macrophages. CCL6 and the human homolog CCL23 were both necessary and sufficient to promote ovarian cancer migration by activating ERK1/2 and PI3K pathways. Importantly, inhibition of CCR1 reduced ovarian cancer colonization. These findings demonstrate a critical mechanism of omental macrophage induced colonization by ovarian cancer cells via CCR1 signaling.
Project description:Macrophages play an important role in the pathological process of stroke. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of infiltrated macrophages from ischemic brain after stroke.
Project description:Ubiquitin specific peptidase 18 (USP18) inhibits type I interferon response and mediates ISG15-deconjugation. Here, we examined the role of USP18 in myeloid-linage cells in tumor development. B16F10 melanoma grown in control or myeloid-specific Usp18 knockout mice were analyzed. Single-cell transcriptomic analysis revealed that the profile of tumor-infiltrated immune cells were altered with Usp18 deletion. We observed that increase in M1-polarized macrophages and decrease in myeloid-derived suppressor cells, resulting enhanced anti-tumor microenvironment in Usp18 conditional knockout mice.
Project description:To test whether Tregs that were newly recruited to tumor-bearing omentum had similar properties to those of adipose resident Tregs, we surgically joined tumor-bearing mice with congenic naive mice, sorted partner-derived Tregs from the omenta and spleens of tumor-bearing (CD45.1+) parabionts on day 14 and performed RNAseq analysis
Project description:Tumor associated macrophages are contributing to local invasion, angiogensis, and metastasis during the progression of many kinds of tumor including glioma We used microrray to study the difference of expression of glioma associated macrophages and normal brain tissue associated macrophages The macrophgages were isolated based on the markers of GFP and F4/80+ from Gl261 glioma and normal brain, RNA were extracted for microarray analysis
Project description:Tumor-associated macrophages (TAMs) represent a major component of the tumor microenvironment that supports tumorigenesis. Here we found that prostate tumors are strongly infiltrated by TAMs expressing the C-X-C chemokine receptor type 2 (CXCR2). Pharmacological blockade of the CXCR2 receptor by a selective antagonist promoted the re-education of TAMs towards a pro-inflammatory phenotype. In vitro gene expression profiling revealed that CXCL2 promotes a pro-tumorigenic (M2-like) functional state in macrophages.
Project description:Tumor associated macrophages are contributing to local invasion, angiogensis, and metastasis during the progression of many kinds of tumor including glioma We used microrray to study the difference of expression of glioma associated macrophages and normal brain tissue associated macrophages